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  • 251.
    Robinson, Matthew R.
    et al.
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia..
    Hemani, Gibran
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia..
    Medina-Gomez, Carolina
    Erasmus Univ, Dept Internal Med, Med Ctr, Rotterdam, Netherlands..
    Mezzavilla, Massimo
    Ist Ricovero & Cura Carattere Sci IRCCS, Inst Maternal & Child Hlth, Trieste, Italy.;Wellcome Trust Sanger Inst, Hinxton, Cambs, England..
    Esko-, Tonu
    Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA USA.;Broad Inst MIT & Harvard, Cambridge, MA USA.;Harvard Univ, Sch Med, Dept Genet, Boston, MA USA..
    Shakhbazov, Konstantin
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia..
    Powell, Joseph E.
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.;Univ Queensland, Translat Res Inst, Diamantina Inst, Brisbane, Qld, Australia..
    Vinkhuyzen, Anna
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia..
    Berndt, Sonja I.
    NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA..
    Gustafsson, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Justice, Anne E.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA..
    Kahali, Bratati
    Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA..
    Locke, Adam E.
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Pers, Tune H.
    Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA USA.;Broad Inst MIT & Harvard, Cambridge, MA USA.;Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.;Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark..
    Vedantam, Sailaja
    Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA USA.;Broad Inst MIT & Harvard, Cambridge, MA USA..
    Wood, Andrew R.
    van Rheenen, Wouter
    Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Neurol & Neurosurg, Utrecht, Netherlands..
    Andreassen, Ole A.
    Univ Oslo, Oslo Univ Hosp, Norwegian Ctr Mental Disorders Res NORMENT, KG Jebsen Ctr Psychosis Res,Div Mental Hlth & Add, Oslo, Norway.;Univ Oslo, Inst Clin Med, Oslo, Norway..
    Gasparini, Paolo
    Ist Ricovero & Cura Carattere Sci IRCCS, Inst Maternal & Child Hlth, Trieste, Italy..
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia..
    van den Berg, Leonard H.
    Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Neurol & Neurosurg, Utrecht, Netherlands..
    Veldink, Jan H.
    Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Neurol & Neurosurg, Utrecht, Netherlands..
    Rivadeneira, Fernando
    Erasmus Univ, Dept Internal Med, Med Ctr, Rotterdam, Netherlands..
    Werge, Thomas M.
    Mental Hlth Devices Copenhagen, MHC Sct Hans, Inst Biol Psychiat, Roskilde, Denmark.;Univ Copenhagen, Dept Clin Med, Fac Hlth & Med Sci, Copenhagen, Denmark.;Lundbeck Fdn Initiat Integrat Psychiat Res iPSYCH, Aarhus, Denmark..
    Abecasis, Goncalo R.
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Boomsma, Dorret I.
    Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands.;Vrije Univ Amsterdam Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands.;Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands..
    Chasman, Daniel I.
    Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.;Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA..
    de Geus, Eco J. C.
    Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands.;Vrije Univ Amsterdam Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands.;Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands..
    Frayling, Timothy M.
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter, Devon, England..
    Hirschhorn, Joel N.
    Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA USA.;Broad Inst MIT & Harvard, Cambridge, MA USA.;Harvard Univ, Sch Med, Dept Genet, Boston, MA USA..
    Hottenga, Jouke Jan
    Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands.;Vrije Univ Amsterdam Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands.;Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands..
    Ingelsson, Erik
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Loos, Ruth J. F.
    Univ Cambridge, Addenbrookes Hosp, Inst Metab Sci, MRC,Epidemiol Unit, Cambridge CB2 2QQ, England.;Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA..
    Magnusson, Patrik K. E.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Martin, Nicholas G.
    QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia..
    Montgomery, Grant W.
    QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia..
    North, Kari E.
    Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.;Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA..
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Spector, Timothy D.
    Kings Coll London, St Thomas Hosp, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England..
    Speliotes, Elizabeth K.
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Goddard, Michael E.
    Dept Primary Ind, Biosci Res Div, Melbourne, Vic, Australia.;Univ Melbourne, Dept Food & Agr Syst, Melbourne, Vic, Australia..
    Yang, Jian
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.;Univ Queensland, Translat Res Inst, Diamantina Inst, Brisbane, Qld, Australia..
    Visscher, Peter M.
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.;Univ Queensland, Translat Res Inst, Diamantina Inst, Brisbane, Qld, Australia..
    Population genetic differentiation of height and body mass index across Europe2015Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 47, nr 11, s. 1357-1362Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Across-nation differences in the mean values for complex traits are common(1-8), but the reasons for these differences are unknown. Here we find that many independent loci contribute to population genetic differences in height and body mass index (BMI) in 9,416 individuals across 14 European countries. Using discovery data on over 250,000 individuals and unbiased effect size estimates from 17,500 sibling pairs, we estimate that 24% (95% credible interval (CI) = 9%, 41%) and 8% (95% CI = 4%, 16%) of the captured additive genetic variance for height and BMI, respectively, reflect population genetic differences. Population genetic divergence differed significantly from that in a null model (height, P < 3.94 x 10(-8); BMI, P < 5.95 x 10(-4)), and we find an among-population genetic correlation for tall and slender individuals (r = -0.80, 95% CI = -0.95, -0.60), consistent with correlated selection for both phenotypes. Observed differences in height among populations reflected the predicted genetic means (r = 0.51; P < 0.001), but environmental differences across Europe masked genetic differentiation for BMI (P < 0.58).

  • 252.
    Roos, Vendela
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Elmstahl, Solve
    Lund Univ, Malmo Univ Hosp, Dept Hlth Sci, Div Geriatr Med, Malmo, Sweden..
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA.;.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Alterations in Multiple Lifestyle Factors in Subjects with the Metabolic Syndrome Independently of Obesity2017Inngår i: Metabolic Syndrome and Related Disorders, ISSN 1540-4196, E-ISSN 1557-8518, Vol. 15, nr 3, s. 118-123Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Many lifestyle factors have been associated with the metabolic syndrome (MetS). However, most of these studies have not considered the potential impact of obesity and have often only investigated one lifestyle factor at the time. We aimed to investigate the interplay between body mass index (BMI) and MetS with respect to multiple lifestyle factors. Methods: BMI and MetS [National Cholesterol Education Program (NCEP)/Adult Treatment Panel III criteria] were assessed in a sample of 18,880 subjects aged 45-75 years from the population-based EpiHealth study. Participants were categorized into six groups according to BMI category (normal weight/BMI <25 kg/m(2), overweight/BMI 25-30 kg/m(2), and obesity/BMI > 30 kg/m(2)) and MetS status (+/-, NCEP criteria). A wide range of lifestyle factors related to physical activity, smoking, alcohol, sleep quality, working conditions, quality of life and stress, and eating patterns were assessed using a questionnaire. Results: Prevalent MetS (23% in the sample) was associated with less physical activity (P < 0.0001), more TV watching (P < 0.0001), more years of smoking (P < 0.0001), lower education level (P = 0.007), and experiencing a poor general quality of life (P < 0.0001). These lifestyle factors were all associated with MetS, independently of each other and independently of BMI. Similar results were generated when number of MetS components and presence/absence of individual MetS components were used as outcomes. Conclusions: This cross-sectional study identified alterations in a number of lifestyle factors associated with MetS independently of each other and independently of BMI. Future longitudinal studies are needed to assess causal and temporal relationships between lifestyle factors and MetS development.

  • 253.
    Roos, Vendela
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Elmstahl, Solve
    Lund Univ, Malmo Univ Hosp, Div Geriatr Med, Dept Hlth Sci, Malmo, Sweden..
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA..
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Metabolic Syndrome Development During Aging with Special Reference to Obesity Without the Metabolic Syndrome2017Inngår i: Metabolic Syndrome and Related Disorders, ISSN 1540-4196, E-ISSN 1557-8518, Vol. 15, nr 1, s. 36-43Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Obesity and its associated metabolic complications continue to increase worldwide. We investigated the development of metabolic syndrome (MetS) during aging in relation to body mass index (BMI) and exercise habits. We assigned special emphasis to the metabolic stability in individuals with obesity, but without MetS, a condition often referred to as metabolically healthy obesity. Materials and Methods: Cross-sectional analysis was carried out in a sample of 19,129 men and women aged 45-75 years from the EpiHealth study. In addition, longitudinal analyses were carried out in the ULSAM study (2322 men at baseline followed from age 50 to age 77) and in the PIVUS study (1016 men and women at baseline followed from age 70 to age 80). Participants were categorized into six groups according to BMI category (normal weight/BMI <25 kg/m(2), overweight/BMI 25-30 kg/m(2), and obesity/BMI >30 kg/m(2)) and MetS status (+/-, National Cholesterol Education Program criteria). Results: MetS prevalence and number of MetS components increased with age in all three samples. The PIVUS study showed that high baseline BMI, low baseline physical activity, and increasing BMI during follow-up were related to increasing MetS prevalence and increasing numbers of MetS components during follow-up. One-third to half of individuals initially belonging to the obesity without MetS category acquired MetS during aging. Conclusions: MetS prevalence increased during aging, especially in individuals with high BMI, low level of physical activity, and weight gain. Obesity without MetS was not a stable condition over time as many of those individuals gained metabolic disturbances during aging.

  • 254.
    Roselli, Carolina
    et al.
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA.
    Chaffin, Mark D.
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA.
    Weng, Lu-Chen
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
    Aeschbacher, Stefanie
    Univ Hosp Basel, Basel, Switzerland;Cardiovasc Res Inst Basel, Basel, Switzerland.
    Ahlberg, Gustav
    Copenhagen Univ Hosp, Dept Cardiol, Heart Ctr, Lab Mol Cardiol,Rigshosp, Copenhagen, Denmark;Univ Copenhagen, Dept Biomed Sci, Danish Natl Res Fdn Ctr Cardiac Arrhythmia, Copenhagen, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark.
    Albert, Christine M.
    Brigham & Womens Hosp, Div Prevent & Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA USA.
    Almgren, Peter
    Lund Univ, Dept Clin Sci, Malmo, Sweden.
    Alonso, Alvaro
    Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA.
    Anderson, Christopher D.
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA;Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA.
    Aragam, Krishna G.
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA;Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA.
    Arking, Dan E.
    Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA.
    Barnard, John
    Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH USA;Cleveland Clin, Dept Cellular & Mol Med, Cleveland, OH USA;Cleveland Clin, Dept Mol Cardiol, Cleveland, OH USA;Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH USA.
    Bartz, Traci M.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit Dept, Seattle, WA 98195 USA;Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
    Benjamin, Emelia J.
    NHLBI, Framingham, MA USA;Boston Univ, Framingham Heart Study, Framingham, MA USA;Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA;Boston Univ, Dept Epidemiol, Sch Publ Hlth, Boston, MA USA.
    Bihlmeyer, Nathan A.
    Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Predoctoral Training Program Human Genet, Baltimore, MD USA.
    Bis, Joshua C.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
    Bloom, Heather L.
    Emory Univ, Div Cardiol, Atlanta, GA 30322 USA;Atlanta VA Med Ctr, Atlanta, GA USA.
    Boerwinkle, Eric
    Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
    Bottinger, Erwin B.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA.
    Brody, Jennifer A.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
    Calkins, Hugh
    Johns Hopkins Univ, Baltimore, MD USA.
    Campbell, Archie
    Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Generat Scotland, Edinburgh, Midlothian, Scotland.
    Cappola, Thomas P.
    Univ Penn, Penn Cardiovasc Inst, Philadelphia, PA 19104 USA;Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
    Carlquist, John
    Intermt Med Ctr, Intermt Heart Inst, Murray, UT USA;Univ Utah, Div Cardiovasc Med, Salt Lake City, UT USA.
    Chasman, Daniel I.
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA;Harvard Med Sch, Boston, MA USA;Harvard Med Sch, Boston, MA USA;Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA;Brigham & Womens Hosp, Div Genet, 75 Francis St, Boston, MA 02115 USA.
    Chen, Lin Y.
    Univ Minnesota, Sch Med, Dept Med, Div Cardiovasc, Minneapolis, MN 55455 USA.
    Chen, Yii-Der Ida
    Harbor UCLA Med Ctr, Dept Pediat, LABioMed, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
    Choi, Eue-Keun
    Seoul Natl Univ Hosp, Seoul, South Korea.
    Choi, Seung Hoan
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA.
    Christophersen, Ingrid E.
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA;Vestre Viken Hosp Trust, Baerum Hosp, Dept Med Res, Drammen, Norway.
    Chung, Mina K.
    Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH USA;Cleveland Clin, Dept Cellular & Mol Med, Cleveland, OH USA;Cleveland Clin, Dept Mol Cardiol, Cleveland, OH USA;Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH USA.
    Cole, John W.
    Baltimore Vet Affairs Med Ctr, Dept Neurol, Baltimore, MD USA;Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA.
    Conen, David
    Univ Hosp Basel, Basel, Switzerland;Cardiovasc Res Inst Basel, Basel, Switzerland;McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Cook, James
    Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.
    Crijns, Harry J.
    Maastricht Univ, Med Ctr, Maastricht, Netherlands;Maastricht Univ, Cardiovasc Res Inst Maastricht, Dept Cardiol, Maastricht, Netherlands.
    Cutler, Michael J.
    Intermt Med Ctr, Intermt Heart Inst, Murray, UT USA.
    Damrauer, Scott M.
    Univ Penn, Dept Surg, Perelman Sch Med, Philadelphia, PA 19104 USA;Corporal Michael Crescenz VA Med Ctr, Dept Surg, Philadelphia, PA USA.
    Daniels, Brian R.
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA.
    Darbar, Dawood
    Univ Illinois, Chicago, IL USA.
    Delgado, Graciela
    Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Heidelberg, Germany.
    Denny, Joshua C.
    Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA.
    Dichgans, Martin
    Univ Hosp, LMU Munich, Inst Stroke & Dementia Res ISD, Munich, Germany;Munich Cluster Syst Neurol SyNergy, Munich, Germany;German Ctr Neurodegenerat Dis DZNE, Munich, Germany.
    Doerr, Marcus
    Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany;Partner Site Greifswald, DZHK German Ctr Cardiovasc Res, Greifswald, Germany.
    Dudink, Elton A.
    Maastricht Univ, Med Ctr, Maastricht, Netherlands;Maastricht Univ, Cardiovasc Res Inst Maastricht, Dept Cardiol, Maastricht, Netherlands.
    Dudley, Samuel C.
    Univ Minnesota, Div Cardiovasc, Minneapolis, MN 55455 USA;Univ Minnesota, Lillehei Heart Inst, Minneapolis, MN USA.
    Esa, Nada
    Univ Massachusetts, Med Sch Worcester, Worcester, MA 01605 USA.
    Esko, Tonu
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.
    Eskola, Markku
    Tampere Univ Hosp, Dept Cardiol, Heart Ctr, Tampere, Finland;Univ Tampere, Fac Med & Life Sci, Tampere, Finland.
    Fatkin, Diane
    Victor Chang Cardiac Res Inst, Darlinghurst, NSW, Australia;St Vincent Hosp, Darlinghurst, NSW, Australia;Univ New South Wales, Fac Med, Kensington, NSW, Australia.
    Felix, Stephan B.
    Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany;Partner Site Greifswald, DZHK German Ctr Cardiovasc Res, Greifswald, Germany.
    Ford, Ian
    Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.
    Franco, Oscar H.
    Erasmus Univ, Med Ctr Rotterdam, Dept Epidemiol, Rotterdam, Netherlands.
    Geelhoed, Bastiaan
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
    Grewal, Raji P.
    St Francis Med Ctr, Dept Neurosci, Trenton, NJ USA;Seton Hall Univ, Sch Hlth & Med Sci, S Orange, NJ USA.
    Gudnason, Vilmundur
    Icelandic Heart Assoc, Kopavogur, Iceland;Univ Iceland, Fac Med, Reykavik, Iceland.
    Guo, Xiuqing
    Harbor UCLA Med Ctr, Dept Pediat, LABioMed, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
    Gupta, Namrata
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA.
    Gustafsson, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Gutmann, Rebecca
    Univ Iowa, Div Cardiovasc Med, Abboud Cardiovasc Res Ctr, Iowa City, IA USA.
    Hamsten, Anders
    Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Cardiovasc Genet & Genom Grp, Stockholm, Sweden.
    Harris, Tamara B.
    NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
    Hayward, Caroline
    Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland.
    Heckbert, Susan R.
    Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA;Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA;Kaiser Permanente, Washington Hlth Res Inst, Seattle, WA USA.
    Hernesniemi, Jussi
    Tampere Univ Hosp, Dept Cardiol, Heart Ctr, Tampere, Finland;Univ Tampere, Fac Med & Life Sci, Tampere, Finland;Univ Tampere, Fac Med & Life Sci, Dept Clin Chem, Fimlab Labs, Tampere, Finland;Univ Tampere, Fac Med & Life Sci, Finnish Cardiovasc Res Ctr Tampere, Tampere, Finland.
    Hocking, Lynne J.
    Univ Aberdeen, Inst Med Sci, Aberdeen, Scotland.
    Hofman, Albert
    Erasmus Univ, Med Ctr Rotterdam, Dept Epidemiol, Rotterdam, Netherlands.
    Horimoto, Andrea R. V. R.
    Univ Sao Paulo, Heart Inst, Lab Genet & Mol Cardiol, Sao Paulo, Brazil.
    Huang, Jie
    Boston VA Res Inst Inc, Boston, MA USA.
    Huang, Paul L.
    Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
    Huffman, Jennifer
    Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. UStanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA.
    Ipek, Esra Gucuk
    Johns Hopkins Univ, Baltimore, MD USA.
    Ito, Kaoru
    RIKEN, Ctr Integrat Med Sci, Lab Cardiovasc Dis, Yokohama, Kanagawa, Japan.
    Jimenez-Conde, Jordi
    Inst Hosp Mar Invest Med, Hosp Mar, Dept Neurol, Neurovasc Res Grp IMIM, Barcelona, Spain;Univ Autonoma Barcelona, Med Dept, Barcelona, Spain.
    Johnson, Renee
    Victor Chang Cardiac Res Inst, Darlinghurst, NSW, Australia.
    Jukema, J. Wouter
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands;Durrer Ctr Cardiogenet Res, Amsterdam, Netherlands;Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands.
    Kaeaeb, Stefan
    Ludwig Maximilians Univ Munchen, Univ Hosp Munich, Dept Med 1, Munich, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany.
    Kahonen, Mika
    Univ Tampere, Fac Med & Life Sci, Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland;Univ Tampere, Fac Med & Life Sci, Finnish Cardiovasc Res Center Tampere, Tampere, Finland.
    Kamatani, Yoichiro
    RIKEN, Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, Japan.
    Kane, John P.
    Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA.
    Kastrati, Adnan
    DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany;Tech Univ Munich, Klin Herz & Kreislauferkrankungen, Deutsch Herzzentrum Munchen, Munich, Germany.
    Kathiresan, Sekar
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA;Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA.
    Katschnig-Winter, Petra
    Med Univ Graz, Dept Neurol, Graz, Austria.
    Kavousi, Maryam
    Erasmus Univ, Med Ctr Rotterdam, Dept Epidemiol, Rotterdam, Netherlands.
    Kessler, Thorsten
    Tech Univ Munich, Klin Herz & Kreislauferkrankungen, Deutsch Herzzentrum Munchen, Munich, Germany.
    Kietselaer, Bas L.
    Maastricht Univ, Med Ctr, Maastricht, Netherlands;Maastricht Univ, Cardiovasc Res Inst Maastricht, Dept Cardiol, Maastricht, Netherlands.
    Kirchhof, Paulus
    Univ Birmingham, Inst Cardiovasc Sci, Birmingham, W Midlands, England;Sandwell & West Birmingham Hosp NHS Trust, Birmingham, W Midlands, England;Univ Hosp Birmingham NHS Fdn Trust, Birmingham, W Midlands, England;AFNET, Munster, Germany.
    Kleber, Marcus E.
    Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Heidelberg, Germany.
    Knight, Stacey
    Intermt Med Ctr, Intermt Heart Inst, Murray, UT USA;Univ Utah, Dept Med, Salt Lake City, UT 84112 USA.
    Krieger, Jose E.
    Univ Sao Paulo, Heart Inst, Lab Genet & Mol Cardiol, Sao Paulo, Brazil.
    Kubo, Michiaki
    RIKEN, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan.
    Launer, Lenore J.
    NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
    Laurikka, Jari
    Univ Tampere, Fac Med & Life Sci, Finnish Cardiovasc Res Center Tampere, Tampere, Finland;Univ Tampere, Fac Med & Life Sci, Tampere Univ Hosp, Heart Ctr,Dept Cardiothoracic Surg, Tampere, Finland.
    Lehtimaki, Terho
    Univ Tampere, Fac Med & Life Sci, Dept Clin Chem, Fimlab Labs, Tampere, Finland;Univ Tampere, Fac Med & Life Sci, Finnish Cardiovasc Res Ctr Tampere, Tampere, Finland.
    Leineweber, Kirsten
    Bayer, Dept Dis Genom, Wuppertal, Germany.
    Lemaitre, Rozenn N.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
    Li, Man
    Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA;Univ Utah, Sch Med, Div Nephrol & Hypertens Internal Med, Salt Lake City, UT USA.
    Lim, Hong Euy
    Korea Univ, Guro Hosp, Seoul, South Korea.
    Lin, Henry J.
    Harbor UCLA Med Ctr, Dept Pediat, LABioMed, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
    Lin, Honghuang
    NHLBI, Framingham, MA USA;Boston Univ, Framingham Heart Study, Framingham, MA USA;Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Lindgren, Cecilia M.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
    Lokki, Marja-Liisa
    Univ Helsinki, Medicum, Transplantat Lab, Helsinki, Finland.
    London, Barry
    Univ Iowa, Div Cardiovasc Med, Abboud Cardiovasc Res Ctr, Iowa City, IA USA.
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY USA.
    Low, Siew-Kee
    RIKEN, Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, Japan.
    Lu, Yingchang
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA.
    Lyytikainen, Leo-Pekka
    Univ Tampere, Fac Med & Life Sci, Dept Clin Chem, Fimlab Labs, Tampere, Finland;Univ Tampere, Fac Med & Life Sci, Finnish Cardiovasc Res Ctr Tampere, Tampere, Finland.
    Macfarlane, Peter W.
    Univ Glasgow, Coll Med Vet & Life Sci, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland.
    Magnusson, Patrik K.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
    Malik, Rainer
    Univ Hosp, LMU Munich, Inst Stroke & Dementia Res ISD, Munich, Germany.
    Mansur, Alfredo J.
    Univ Sao Paulo, Heart Inst, Sao Paulo, Brazil.
    Marcus, Gregory M.
    Univ Calif San Francisco, Div Cardiol, San Francisco, CA 94143 USA.
    Margolin, Lauren
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA.
    Margulies, Kenneth B.
    Univ Penn, Penn Cardiovasc Inst, Philadelphia, PA 19104 USA;Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
    Maerz, Winfried
    Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria;Synlab Serv GmbH, Synlab Acad, Mannheim, Germany.
    McManus, David D.
    Univ Massachusetts, Med Sch Worcester, Worcester, MA 01605 USA.
    Melander, Olle
    Lund Univ, Dept Internal Med Clin Sci, Malmo, Sweden.
    Mohanty, Sanghamitra
    St Davids Med Ctr, Texas Cardiac Arrhythmia Inst, Austin, TX USA;Dell Med Sch, Austin, TX USA.
    Montgomery, Jay A.
    Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA.
    Morley, Michael P.
    Univ Penn, Penn Cardiovasc Inst, Philadelphia, PA 19104 USA;Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
    Morris, Andrew P.
    Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.
    Mueller-Nurasyid, Martina
    Ludwig Maximilians Univ Munchen, Univ Hosp Munich, Dept Med 1, Munich, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, Neuherberg, Germany.
    Natale, Andrea
    St Davids Med Ctr, Texas Cardiac Arrhythmia Inst, Austin, TX USA;Dell Med Sch, Austin, TX USA.
    Nazarian, Saman
    Univ Penn, Philadelphia, PA USA.
    Neumann, Benjamin
    Ludwig Maximilians Univ Munchen, Univ Hosp Munich, Dept Med 1, Munich, Germany.
    Newton-Cheh, Christopher
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA;Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA.
    Niemeijer, Maartje N.
    Erasmus Univ, Med Ctr Rotterdam, Dept Epidemiol, Rotterdam, Netherlands.
    Nikus, Kjell
    Tampere Univ Hosp, Dept Cardiol, Heart Ctr, Tampere, Finland;Univ Tampere, Fac Med & Life Sci, Tampere, Finland.
    Nilsson, Peter
    Lund Univ, Dept Clin Sci, Malmo, Sweden;Skane Univ Hosp, Malmo, Sweden.
    Noordam, Raymond
    Leiden Univ, Med Ctr, Dept Internal Med, Sect Gerontol & Geriatr, Leiden, Netherlands.
    Oellers, Heidi
    Atrial Fibrillat NETwork, Munster, Germany.
    Olesen, Morten S.
    Copenhagen Univ Hosp, Dept Cardiol, Heart Ctr, Lab Mol Cardiol,Rigshosp, Copenhagen, Denmark;Univ Copenhagen, Dept Biomed Sci, Danish Natl Res Fdn Ctr Cardiac Arrhythmia, Copenhagen, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark.
    Orho-Melander, Marju
    Lund Univ, Dept Clin Sci, Malmo, Sweden.
    Padmanabhan, Sandosh
    Univ Glasgow, BHF Glasgow Cardiovasc Res Ctr, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
    Pak, Hui-Nam
    Yonsei Univ Hlth Syst, Seoul, South Korea.
    Pare, Guillaume
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada;McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada.
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Pera, Joanna
    Jagiellonian Univ, Med Coll, Fac Med, Dept Neurol, Krakow, Poland.
    Pereira, Alexandre
    Univ Sao Paulo, Heart Inst, Lab Genet & Mol Biol, Sao Paulo, Brazil;Harvard Med Sch, Dept Genet, Boston, MA USA.
    Porteous, David
    Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Generat Scotland, Edinburgh, Midlothian, Scotland.
    Psaty, Bruce M.
    Kaiser Permanente, Washington Hlth Res Inst, Seattle, WA USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA;Univ Washington, Dept Epidemiol & Hlth Serv, Seattle, WA 98195 USA.
    Pulit, Sara L.
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA;Univ Utrecht, Univ Med Ctr Utrecht, Ctr Mol Med, Dept Genet, Utrecht, Netherlands;Univ Oxford, Big Data Inst, Li Ka Shing Ctr Hlth Informat & Discovery, Oxford, England.
    Pullinger, Clive R.
    Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA.
    Rader, Daniel J.
    Univ Penn, Perelman Sch Med, Dept Med, Div Cardiovasc Med, Philadelphia, PA USA.
    Refsgaard, Lena
    Copenhagen Univ Hosp, Dept Cardiol, Heart Ctr, Lab Mol Cardiol,Rigshosp, Copenhagen, Denmark;Univ Copenhagen, Dept Biomed Sci, Danish Natl Res Fdn Ctr Cardiac Arrhythmia, Copenhagen, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark.
    Ribases, Marta
    Univ Autonoma Barcelona, Vall dHebron Res Inst VHIR, Grp Psychiat Mental Hlth & Addict, Psychiatr Genet Unit, Barcelona, Spain;Hosp Univ Vall dHebron, Dept Psychiat, Barcelona, Spain;Inst Salud Carlos III, Biomed Network Res Ctr Mental Hlth CIBERSAM, Madrid, Spain.
    Ridker, Paul M.
    Brigham & Womens Hosp, Div Prevent & Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA USA.
    Rienstra, Michiel
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
    Risch, Lorenz
    Univ Bern, Univ Inst Clin Chem, Bern, Switzerland;Lab Med Zentrum Dr Risch, Schaan, Liechtenstein.
    Roden, Dan M.
    Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA.
    Rosand, Jonathan
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA;Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA.
    Rosenberg, Michael A.
    Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA;Univ Colorado, Sch Med, Aurora, CO USA.
    Rost, Natalia
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA;Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Boston, MA 02114 USA.
    Rotter, Jerome I.
    Harbor UCLA Med Ctr, LABioMed, Inst Translat Genom & Populat Sci, Dept Pediat, Torrance, CA 90509 USA;Harbor UCLA Med Ctr, LABioMed, Dept Med, Torrance, CA 90509 USA.
    Saba, Samir
    Univ Pittsburgh, Div Cardiol, Pittsburgh, PA USA.
    Sandhu, Roopinder K.
    Univ Alberta, Div Cardiol, Edmonton, AB, Canada.
    Schnabel, Renate B.
    Univ Heart Ctr Hamburg, Dept Gen & Intervent Cardiol, Hamburg, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Hamburg Kiel Lubeck, Hamburg, Germany.
    Schramm, Katharina
    Ludwig Maximilians Univ Munchen, Univ Hosp Munich, Dept Med 1, Munich, Germany;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, Neuherberg, Germany.
    Schunkert, Heribert
    DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany;Tech Univ Munich, Klin Herz & Kreislauferkrankungen, Deutsch Herzzentrum Munchen, Munich, Germany.
    Schurman, Claudia
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA.
    Scott, Stuart A.
    Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA.
    Seppala, Ilkka
    Univ Tampere, Fac Med & Life Sci, Dept Clin Chem, Fimlab Labs, Tampere, Finland;Univ Tampere, Fac Med & Life Sci, Finnish Cardiovasc Res Ctr Tampere, Tampere, Finland.
    Shaffer, Christian
    Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA.
    Shah, Svati
    Duke Univ, Sch Med, Dept Med, Div Cardiol, Durham, NC 27706 USA.
    Shalaby, Alaa A.
    Univ Pittsburgh, Div Cardiol, Pittsburgh, PA USA;Pittsburgh VA Healthcare Syst, Cardiol Div, Pittsburgh, PA USA.
    Shim, Jaemin
    Korea Univ, Anam Hosp, Seoul, South Korea.
    Shoemaker, M. Benjamin
    Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA.
    Siland, Joylene E.
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
    Sinisalo, Juha
    Univ Helsinki, Cent Hosp, Heart & Lung Ctr HUS, Helsinki, Finland.
    Sinner, Moritz F.
    Ludwig Maximilians Univ Munchen, Univ Hosp Munich, Dept Med 1, Munich, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany.
    Slowik, Agnieszka
    Jagiellonian Univ, Med Coll, Fac Med, Dept Neurol, Krakow, Poland.
    Smith, Albert V.
    Icelandic Heart Assoc, Kopavogur, Iceland;Univ Iceland, Fac Med, Reykavik, Iceland.
    Smith, Blair H.
    Univ Dundee, Div Populat Hlth Sci, Dundee, Scotland.
    Smith, J. Gustav
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA;Lund Univ, Dept Cardiol Clin Sci, Lund, Sweden;Skane Univ Hosp, Lund, Sweden.
    Smith, Jonathan D.
    Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH USA;Cleveland Clin, Dept Cellular & Mol Med, Cleveland, OH USA;Cleveland Clin, Dept Mol Cardiol, Cleveland, OH USA;Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH USA.
    Smith, Nicholas L.
    Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA;Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA;Kaiser Permanente, Washington Hlth Res Inst, Seattle, WA USA.
    Soliman, Elsayed Z.
    Wake Forest Sch Med, Epidemiol Cardiol Res Ctr EPICARE, Winston Salem, NC USA.
    Sotoodehnia, Nona
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA;Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
    Stricker, Bruno H.
    Erasmus Univ, Med Ctr Rotterdam, Dept Epidemiol & Internal Med, Rotterdam, Netherlands;Inspectorate Hlth Care, Utrecht, Netherlands.
    Sun, Albert
    Duke Univ, Sch Med, Dept Med, Div Cardiol, Durham, NC 27706 USA.
    Sun, Han
    Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH USA;Cleveland Clin, Dept Cellular & Mol Med, Cleveland, OH USA;Cleveland Clin, Dept Mol Cardiol, Cleveland, OH USA;Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH USA.
    Svendsen, Jesper H.
    Copenhagen Univ Hosp, Dept Cardiol, Heart Ctr, Lab Mol Cardiol,Rigshosp, Copenhagen, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark.
    Tanaka, Toshihiro
    Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Human Genet & Dis Div, Tokyo, Japan.
    Tanriverdi, Kahraman
    Univ Massachusetts, Med Sch Worcester, Worcester, MA 01605 USA.
    Taylor, Kent D.
    Harbor UCLA Med Ctr, Dept Pediat, LABioMed, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
    Teder-Laving, Maris
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.
    Teumer, Alexander
    Partner Site Greifswald, DZHK German Ctr Cardiovasc Res, Greifswald, Germany;Univ Med Greifswald, Inst Community Med, Greifswald, Germany.
    Theriault, Sebastien
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada;McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada.
    Trompet, Stella
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands;Leiden Univ, Med Ctr, Dept Internal Med, Sect Gerontol & Geriatr, Leiden, Netherlands.
    Tucker, Nathan R.
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
    Tveit, Arnljot
    Vestre Viken Hosp Trust, Baerum Hosp, Dept Med Res, Drammen, Norway;Univ Oslo, Inst Clin Med, Oslo, Norway.
    Uitterlinden, Andre G.
    Erasmus Univ, Med Ctr Rotterdam, Dept Epidemiol & Internal Med, Rotterdam, Netherlands.
    Van Der Harst, Pim
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
    Van Gelder, Isabelle C.
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
    Van Wagoner, David R.
    Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH USA;Cleveland Clin, Dept Cellular & Mol Med, Cleveland, OH USA;Cleveland Clin, Dept Mol Cardiol, Cleveland, OH USA;Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH USA.
    Verweij, Niek
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
    Vlachopoulou, Efthymia
    Univ Helsinki, Medicum, Transplantat Lab, Helsinki, Finland.
    Voelker, Uwe
    Partner Site Greifswald, DZHK German Ctr Cardiovasc Res, Greifswald, Germany;Univ Med Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Gen, Greifswald, Germany.
    Wang, Biqi
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
    Weeke, Peter E.
    Copenhagen Univ Hosp, Dept Cardiol, Heart Ctr, Lab Mol Cardiol,Rigshosp, Copenhagen, Denmark;Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA.
    Weijs, Bob
    Maastricht Univ, Med Ctr, Maastricht, Netherlands;Maastricht Univ, Cardiovasc Res Inst Maastricht, Dept Cardiol, Maastricht, Netherlands.
    Weiss, Raul
    Ohio State Univ, Div Cardiovasc Med, Columbus, OH 43210 USA.
    Weiss, Stefan
    Partner Site Greifswald, DZHK German Ctr Cardiovasc Res, Greifswald, Germany;Univ Med Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Gen, Greifswald, Germany.
    Wells, Quinn S.
    Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA.
    Wiggins, Kerri L.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
    Wong, Jorge A.
    McMaster Univ, Div Cardiol Hamilton Hlth Sci, Hamilton, ON, Canada.
    Woo, Daniel
    Univ Cincinnati, Coll Med, Cincinnati, OH USA.
    Worrall, Bradford B.
    Univ Virginia Hlth Syst, Dept Neurol, Charlottesville, VA USA;Univ Virginia Hlth Syst, Dept Publ Hlth Sci, Charlottesville, VA USA.
    Yang, Pil-Sung
    Yonsei Univ Hlth Syst, Seoul, South Korea.
    Yao, Jie
    Harbor UCLA Med Ctr, Dept Pediat, LABioMed, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
    Yoneda, Zachary T.
    Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA.
    Zeller, Tanja
    Univ Heart Ctr Hamburg, Dept Gen & Intervent Cardiol, Hamburg, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Hamburg Kiel Lubeck, Hamburg, Germany.
    Zeng, Lingyao
    Tech Univ Munich, Klin Herz & Kreislauferkrankungen, Deutsch Herzzentrum Munchen, Munich, Germany.
    Lubitz, Steven A.
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA;Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
    Lunetta, Kathryn L.
    NHLBI, Framingham, MA USA;Boston Univ, Framingham Heart Study, Framingham, MA USA;Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
    Ellinor, Patrick T.
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA;Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
    Multi-ethnic genome-wide association study for atrial fibrillation2018Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 50, nr 9, s. 1225-1233Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Atrial fibrillation (AF) affects more than 33 million individuals worldwide(1) and has a complex heritability(2). We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.

  • 255.
    Ruge, Toralph
    et al.
    Karolinska Inst, Dept Med, Stockholm, Sweden; Karolinska Inst, Dept Med, Stockholm, Sweden.
    Carlsson, Axel C
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, Huddinge, Sweden.
    Ingelsson, Erik
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Stanford Univ, Sch Med, Div Cardiovasc Med, Stanford, CA USA.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning Dalarna. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, Huddinge, Sweden.
    Circulating endostatin and the incidence of heart failure.2018Inngår i: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 52, nr 5, s. 244-249Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Circulating levels of endostatin are elevated in many underlying conditions leading to heart failure such as hypertension, diabetes, chronic kidney disease and ischemic heart disease. Yet, the association between endostatin and the incidence of heart failure has not been reported previously in the community.

    Design: We investigated the longitudinal association between serum endostatin levels and incident heart failure in two community-based cohorts of elderly: Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS, n = 966; mean age 70 years, 51% women, 81 events, mean follow-up 10 years) and Uppsala Longitudinal Study of Adult Men (ULSAM, n = 747 men; mean age 78 years, 98 heart failure events, mean follow-up 8 years). We also investigated the cross-sectional association between endostatin and echocardiographic left ventricular systolic function and diastolic function (ejection fraction and E/A-ratio, respectively).

    Results: Higher serum endostatin was associated with an increased risk for heart failure in both cohorts after adjustment for established heart failure risk factors, glomerular filtration rate and N-terminal pro-brain natriuretic peptide (NT-proBNP) (PIVUS: multivariable hazard ratio (HR) per 1-standard deviation (SD) increase, HR 1.46 (95%CI, 1.17-1.82, p < .001); ULSAM: HR 1.29 (95%CI, 1.00-1.68, p < .05). In cross-sectional analyses at baseline, higher endostatin was significantly associated with both worsened left ventricular systolic and diastolic function in both cohorts.

    Conclusion: Higher serum endostatin was associated with left ventricular dysfunction and an increased heart failure risk in two community-based cohorts of elderly. Our findings encourage further experimental studies that investigate the role of endostatin in the development of heart failure.

  • 256. Ruge, Toralph
    et al.
    Carlsson, Axel C
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Larsson, Tobias E
    Carrero, Juan-Jesús
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Endostatin Level is Associated with Kidney Injury in the Elderly: Findings from Two Community-Based Cohorts2014Inngår i: American Journal of Nephrology, ISSN 0250-8095, E-ISSN 1421-9670, Vol. 40, nr 5, s. 417-424Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: We aimed to investigate the associations between circulating endostatin and the different aspects of renal dysfunction, namely, estimated (cystatin C) glomerular filtration rate (GFR) and urine albumin-creatinine ratio (ACR).

    Methods: Two independent longitudinal community-based cohorts of elderly. ULSAM, n = 786 men; age 78 years; median GFR 74 ml/min/1.73 m(2); median ACR 0.80 mg/mmol); and PIVUS, n = 815; age 75 years; 51% women; median GFR; 67 ml/min/1.73 m(2); median ACR 1.39 mg/mmol. Cross-sectional associations between the endostatin levels and GFR as well as ACR, and longitudinal association between endostatin at baseline and incident CKD (defined as GFR <60 ml/min/1.73 m(2)) were assessed.

    Results: In cross-sectional regression analyses adjusting for age, gender, inflammation, and cardiovascular risk factors, serum endostatin was negatively associated with GFR (ULSAM: B-coefficient per SD increase -0.51, 95% CI (-0.57, -0.45), p < 0.001; PIVUS -0.47, 95% CI (-0.54, -0.41), p < 0.001) and positively associated with ACR (ULSAM: B-coefficient per SD increase 0.24, 95% CI (0.15, 0.32), p < 0.001; PIVUS 0.13, 95% CI (0.06-0.20), p < 0.001) in both cohorts. Moreover, in longitudinal multivariable analyses, higher endostatin levels were associated with increased risk for incident CKD defined as GFR <60 ml/min/1.73 m(2) at re-investigations in both ULSAM (odds ratio per SD increase of endostatin 1.39 (95% CI 1.01-1.90) and PIVUS 1.68 (95% CI 1.36-2.07)).

    Conclusions: Higher circulating endostatin is associated with lower GFR and higher albuminuria and independently predicts incident CKD in elderly subjects. Further studies are warranted to investigate the underlying mechanisms linking endostatin to kidney pathology, and to evaluate the clinical relevance of our findings.

  • 257.
    Saleheen, Danish
    et al.
    Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.;Ctr Noncommunicable Dis, Karachi, Pakistan..
    Zhao, Wei
    Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA..
    Young, Robin
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England..
    Nelson, Christopher P.
    Univ Leicester, Dept Cardiovascular Sci, Leicester, Leics, England..
    Ho, WeangKee
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England..
    Ferguson, Jane F.
    Vanderbilt Univ, Dept Med, Cardiol Div, Nashville, TN USA..
    Rasheed, Asif
    Ctr Noncommunicable Dis, Karachi, Pakistan..
    Ou, Kristy
    Vanderbilt Univ, Dept Med, Cardiol Div, Nashville, TN USA..
    Nurnberg, Sylvia T.
    Univ Penn, Perelman Sch Med, Dept Med, Div Translat Med & Human Genet, Philadelphia, PA 19104 USA..
    Bauer, Robert C.
    Columbia Univ, Med Ctr, Dept Med, Cardiol Div, New York, NY USA.;Columbia Univ, Med Ctr, Irving Inst Clin & Translat Res, New York, NY USA..
    Goel, Anuj
    Univ Oxford, Radcliffe Dept Med, Div Cardiovasc Med, Oxford, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Do, Ron
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA..
    Stewart, Alexandre F. R.
    Univ Ottawa, Heart Inst, Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada..
    Hartiala, Jaana
    Univ Southern Calif, Keck Sch Med, Inst Med Genet, Los Angeles, CA USA.;Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA..
    Zhang, Weihua
    Imperial Coll London, Dept Epidemiol & Biostat, London, England.;Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England..
    Thorleifsson, Gudmar
    deCODE Genet, Sturlugata 8, IS-101 Reykjavik, Iceland.;Univ Iceland, Sch Med, Reykjavik, Iceland..
    Strawbridge, Rona J.
    Karolinska Inst, Cardiovasc Med Unit, Dept Med Solna, Stockholm, Sweden..
    Sinisalo, Juha
    Helsinki Univ Cent Hosp HUCH Heart & Lung Ctr, Helsinki, Uusimaa, Finland..
    Kanoni, Stavroula
    William Harvey Res Inst, Barts, England.;Queen Mary Univ London, London Sch Med & Dent, London, England..
    Sedaghat, Sanaz
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Marouli, Eirini
    William Harvey Res Inst, Barts, England.;Queen Mary Univ London, London Sch Med & Dent, London, England.;Harokopio Univ, Dept Dietet Nutr, Athens, Greece..
    Kristiansson, Kati
    Natl Inst Hlth & Welf, Helsinki, Finland..
    Zhao, Jing Hua
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge Biomed Campus, Cambridge, England..
    Scott, Robert
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge Biomed Campus, Cambridge, England..
    Gauguier, Dominique
    INSERM, UMRS1138, Ctr Rech Cordeliers, Paris, France..
    Shah, Svati H.
    Duke Univ, Med Ctr, Dept Med, Div Cardiol, Durham, NC 27710 USA..
    Smith, Albert Vernon
    Iceland Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    van Zuydam, Natalie
    Univ Dundee, Med Res Inst, Ninewells Hosp & Med Sch, Dundee, Scotland..
    Cox, Amanda J.
    Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA..
    Willenborg, Christina
    Univ Lubeck, Inst Integrat & Experimentelle Genom, Lubeck, Germany.;DZHK German Res Ctr Cardiovasc Res, Hamburg, Germany..
    Kessler, Thorsten
    Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany.;Klinikum Rechts Der Isar, Munich, Germany..
    Zeng, Lingyao
    Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany.;DZHK German Res Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany..
    Province, Michael A.
    Washington Univ, Sch Med, Dept Genet, St Louis, MO USA..
    Ganna, Andrea
    Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA.;Harvard Med Sch, Boston, MA 02114 USA.;Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    White, Charles C.
    Boston Univ, Sch Publ Hlth Framingham Heart Study, Dept Biostat, Boston, MA 02215 USA..
    Joensuu, Anni
    Natl Inst Hlth & Welf, Helsinki, Finland.;Univ Helsinki, Inst Mol Med, Helsinki, Finland..
    Kleber, Marcus Edi
    Heidelberg Univ, Mannheim Med Fac, Dept Med, Heidelberg, Germany..
    Hall, Alistair S.
    Univ Leeds, Leeds Inst Genet Hlth & Therapeut, Leeds, W Yorkshire, England..
    Maerz, Winfried
    Synlab Serv GmbH, Synlab Acad, Mannheim, Germany.;Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria..
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Helsinki, Finland..
    O'Donnell, Christopher
    NHLBI, Bldg 10, Bethesda, MD 20892 USA.;NIH, Framingham Heart Study, Bethesda, MD USA..
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Feitosa, Mary F.
    Washington Univ, Sch Med, Dept Genet, St Louis, MO USA..
    Erdmann, Jeanette
    Univ Lubeck, Inst Integrat & Experimentelle Genom, Lubeck, Germany.;DZHK German Res Ctr Cardiovasc Res, Hamburg, Germany..
    Bowden, Donald W.
    Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA..
    Palmer, Colin N. A.
    Univ Dundee, Med Res Inst, Ninewells Hosp & Med Sch, Dundee, Scotland..
    Gudnason, Vilmundur
    Iceland Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    De Faire, Ulf
    Karolinska Inst, Inst Environm Med, Div Cardiovasc Epidemiol, Stockholm, Sweden..
    Zalloua, Pierre
    Lebanese Amer Univ, Sch Med, Beirut, Lebanon..
    Wareham, Nicholas
    INSERM, UMRS1138, Ctr Rech Cordeliers, Paris, France..
    Thompson, John R.
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
    Kuulasmaa, Kari
    Natl Inst Hlth & Welf, Helsinki, Finland..
    Dedoussis, George
    Harokopio Univ, Dept Dietet Nutr, Athens, Greece..
    Perola, Markus
    Natl Inst Hlth & Welf, Helsinki, Finland.;Univ Helsinki, Inst Mol Med, Helsinki, Finland..
    Dehghan, Abbas
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Chambers, John C.
    Imperial Coll London, Dept Epidemiol & Biostat, London, England.;Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England.;Imperial Coll Healthcare NHS Trust, London, England..
    Kooner, Jaspal
    Imperial Coll London, Dept Epidemiol & Biostat, London, England.;Imperial Coll Healthcare NHS Trust, London, England.;Imperial Coll London, Natl Heart & Lung Inst, Cardiovasc Sci, London, England..
    Allayee, Hooman
    Univ Southern Calif, Keck Sch Med, Inst Med Genet, Los Angeles, CA USA.;Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA..
    Deloukas, Panos
    William Harvey Res Inst, Barts, England.;Queen Mary Univ London, London Sch Med & Dent, London, England.;King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah, Saudi Arabia..
    McPherson, Ruth
    Univ Ottawa, Heart Inst, Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada..
    Stefansson, Kari
    deCODE Genet, Sturlugata 8, IS-101 Reykjavik, Iceland.;Univ Iceland, Sch Med, Reykjavik, Iceland..
    Schunkert, Heribert
    Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany.;DZHK German Res Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany..
    Kathiresan, Sekar
    MIT, Broad Inst, Cambridge, MA 02139 USA.;Harvard Univ, Cambridge, MA 02138 USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Harvard Med Sch, Dept Med, Boston, MA USA..
    Farrall, Martin
    Univ Oxford, Radcliffe Dept Med, Div Cardiovasc Med, Oxford, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Frossard, Philippe Marcel
    Ctr Noncommunicable Dis, Karachi, Pakistan..
    Rader, Daniel J.
    Univ Penn, Dept Genet, Philadelphia, PA 19104 USA.;Univ Penn, Perelman Sch Med, Dept Med, Div Translat Med & Human Genet, Philadelphia, PA 19104 USA..
    Samani, Nilesh J.
    Univ Leicester, Dept Cardiovascular Sci, Leicester, Leics, England..
    Reilly, Muredach P.
    Columbia Univ, Med Ctr, Dept Med, Cardiol Div, New York, NY USA.;Columbia Univ, Med Ctr, Irving Inst Clin & Translat Res, New York, NY USA..
    Loss of Cardioprotective Effects at the ADAMTS7 Locus as a Result of Gene-Smoking Interactions2017Inngår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 135, nr 24, s. 2336-2353Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Common diseases such as coronary heart disease (CHD) are complex in etiology. The interaction of genetic susceptibility with lifestyle factors may play a prominent role. However, gene-lifestyle interactions for CHD have been difficult to identify. Here, we investigate interaction of smoking behavior, a potent lifestyle factor, with genotypes that have been shown to associate with CHD risk.

    METHODS: We analyzed data on 60 919 CHD cases and 80 243 controls from 29 studies for gene-smoking interactions for genetic variants at 45 loci previously reported to be associated with CHD risk. We also studied 5 loci associated with smoking behavior. Study-specific gene-smoking interaction effects were calculated and pooled using fixed-effects meta-analyses. Interaction analyses were declared to be significant at a P value of < 1.0x10-3 (Bonferroni correction for 50 tests).

    RESULTS: We identified novel gene-smoking interaction for a variant upstream of the ADAMTS7 gene. Every T allele of rs7178051 was associated with lower CHD risk by 12% in never-smokers (P= 1.3x10(-16)) in comparison with 5% in ever-smokers (P= 2.5x10-4), translating to a 60% loss of CHD protection conferred by this allelic variation in people who smoked tobacco (interaction P value= 8.7x10-5). The protective T allele at rs7178051 was also associated with reduced ADAMTS7 expression in human aortic endothelial cells and lymphoblastoid cell lines. Exposure of human coronary artery smooth muscle cells to cigarette smoke extract led to induction of ADAMTS7.

    CONCLUSIONS: Allelic variation at rs7178051 that associates with reduced ADAMTS7 expression confers stronger CHD protection in never-smokers than in ever-smokers. Increased vascular ADAMTS7 expression may contribute to the loss of CHD protection in smokers.

  • 258.
    Salihovic, Samira
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. MTM Research Centre, School of Science and Technology, Örebro University.
    Fall, Tove
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Ganna, Andrea
    Broeckling, Corey D
    Prenni, Jessica E
    Hyötyläinen, Tuulia
    Kärrman, Anna
    Lind, P. Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Ingelsson, Erik
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Identification of metabolic profiles associated with human exposure to perfluoroalkyl substances.2019Inngår i: Journal of Exposure Science and Environmental Epidemiology, ISSN 1559-0631, E-ISSN 1559-064X, Vol. 29, nr 2, s. 196-205Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Recent epidemiological studies suggest that human exposure to perfluoroalkyl substances (PFASs) may be associated with type 2 diabetes and other metabolic phenotypes. To gain further insights regarding PFASs exposure in humans, we here aimed to characterize the associations between different PFASs and the metabolome. In this cross-sectional study, we investigated 965 individuals from Sweden (all aged 70 years, 50% women) sampled in 2001-2004. PFASs were analyzed in plasma using isotope-dilution ultra-pressure liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). Non-target metabolomics profiling was performed in plasma using UPLC coupled to time-of-flight mass spectrometry (UPLC-QTOFMS) operated in positive electrospray mode. Multivariate linear regression analysis was used to investigate associations between circulating levels of PFASs and metabolites. In total, 15 metabolites, predominantly from lipid pathways, were associated with levels of PFASs following adjustment for sex, smoking, exercise habits, education, energy, and alcohol intake, after correction for multiple testing. Perfluorononanoic acid (PFNA) and perfluoroundecanoic acid (PFUnDA) were strongly associated with multiple glycerophosphocholines and fatty acids including docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA). We also found that the different PFASs evaluated were associated with distinctive metabolic profiles, suggesting potentially different biochemical pathways in humans.

  • 259.
    Salihovic, Samira
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. MTM Research Centre, School of Science and Technology, Örebro University, SE-701 82 Örebro, Sweden.
    Kärrman, Anna
    MTM Research Centre, School of Science and Technology, Örebro University, SE-701 82 Örebro, Sweden.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Lind, P. Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Lindström, Gunilla
    MTM Research Centre, School of Science and Technology, Örebro University, SE-701 82 Örebro, Sweden.
    van Bavel, Bert
    MTM Research Centre, School of Science and Technology, Örebro University, SE-701 82 Örebro, Sweden.
    Perfluoroalkyl substances (PFAS) including structural PFOS isomers in plasma from elderly men and women from Sweden: Results from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS)2015Inngår i: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 82, s. 21-27Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Per- and polyfluoroalkyl substances (PFASs) are a class of compounds with unique chemical properties that have been shown useful in a wide variety of applications because they provide materials with reduced surface tension and exceptional non-stick properties. PFASs are commonly found in impregnation materials, coatings of papers and textiles, fire-fighting foams, pesticides, and cleaning agents. The potential for human exposure to PFASs is high because of their widespread distribution. The aim of this study was to investigate levels of PFASs in men and women from Sweden and to assess the influence of gender and parity among women. Levels of 13 PFASs were determined in plasma samples collected during 2001-2004 from 1016 (507 women) 70 year-old participants from the population-based Prospective Study of the Vasculature in Uppsala Seniors (PIVUS). The PFASs studied were nine perfluorinated carboxylic acids (PFCAs), four perfluorinated sulfonic acids (PFSAs) and perfluorooctane sulfonamide (PFOSA). In addition, structural isomers of perfluorooctane sulfonic acid (PFOS) were determined in a subset of 398 individuals. The detection rates were high and the majority of the studied compounds were detected in more than 75% of the participants. Levels of the selected analytes were found to be similar to other studies of non-occupationally exposed populations. Gender differences were observed in levels of PFHpA which was higher in men, while PFHxS was higher in women. Parity among women was shown to have a minor effect on PFAS concentrations and we found primi- and multiparous women to have slightly lower levels of PFUnDA when compared to nulliparous women.

  • 260.
    Salihovic, Samira
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Orebro Univ, Sch Sci & Technol, MTM Res Ctr, Orebro, Sweden.
    Stubleski, Jordan
    Orebro Univ, Sch Sci & Technol, MTM Res Ctr, Orebro, Sweden.
    Kärrman, Anna
    Orebro Univ, Sch Sci & Technol, MTM Res Ctr, Orebro, Sweden.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Fall, Tove
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Lind, P. Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Changes in markers of liver function in relation to changes in perfluoroalkyl substances - A longitudinal study2018Inngår i: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 117, s. 196-203Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: While it is known that perfluoroalkyl substances (PFASs) induce liver toxicity in experimental studies, the evidence of an association in humans is inconsistent.

    Objective: The main aim of the present study was to examine the association of PFAS concentrations and markers of liver function using panel data.

    Methods: We investigated 1002 individuals from Sweden (50% women) at ages 70, 75 and 80 in 2001-2014. Eight PFASs were measured in plasma using isotope dilution ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS). Bilirubin and hepatic enzymes alanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma-glutamyltransferase (GGT) were determined in serum using an immunoassay methodology. Mixed-effects linear regression models were used to examine the relationship between the changes in markers of liver function and changes in PFAS levels.

    Results: The changes in majority of PFAS concentrations were positively associated with the changes in activity of ALT, ALP, and GGT and inversely associated with the changes in circulating bilirubin after adjustment for gender and the time-updated covariates LDL- and HDL-cholesterol, serum triglycerides, BMI, statin use, smoking, fasting glucose levels and correction for multiple testing. For example, changes in perfluorononanoic acid (PFNA) were associated with the changes liver function markers beta(BILIRUBIN) = -1.56, 95% confidence interval (CI) -1.93 to -1.19, beta(ALT)= 0.04, 95% CI 0.03-0.06, and beta(ALP)= 0.11, 95% CI 0.06-0.15.

    Conclusion: Our longitudinal assessment established associations between changes in markers of liver function and changes in plasma PFAS concentrations. These findings suggest a relationship between low-dose background PFAS exposure and altered liver function in the general population.

  • 261.
    Schmidt, Amand F.
    et al.
    UCL, Inst Cardiovasc Sci, 222 Euston Rd, London NW1 2DA, England;Univ Utrecht, Univ Med Ctr Utrecht, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands;UCLs BHF Res Accelerator Ctr, London, England.
    Holmes, Michael V.
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Med Res Council Populat Hlth Res Unit, Oxford, England;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit CTSU, Oxford, England.
    Preiss, David
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Med Res Council Populat Hlth Res Unit, Oxford, England;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit CTSU, Oxford, England.
    Swerdlow, Daniel I.
    UCL, Inst Cardiovasc Sci, 222 Euston Rd, London NW1 2DA, England;Imperial Coll London, Dept Med, London, England.
    Denaxas, Spiros
    UCLs BHF Res Accelerator Ctr, London, England;UCL, Hlth Data Res UK, 222 Euston Rd, London NW1 2DA, England;UCL, Inst Hlth Informat, 222 Euston Rd, London NW1 2DA, England;British Lib, Alan Turing Inst, 96 Euston Rd, London NW1 2DB, England.
    Fatemifar, Ghazaleh
    UCLs BHF Res Accelerator Ctr, London, England;UCL, Hlth Data Res UK, 222 Euston Rd, London NW1 2DA, England;UCL, Inst Hlth Informat, 222 Euston Rd, London NW1 2DA, England.
    Faraway, Rupert
    UCL, Inst Cardiovasc Sci, 222 Euston Rd, London NW1 2DA, England.
    Finan, Chris
    UCL, Inst Cardiovasc Sci, 222 Euston Rd, London NW1 2DA, England;UCLs BHF Res Accelerator Ctr, London, England.
    Valentine, Dennis
    UCLs BHF Res Accelerator Ctr, London, England;UCL, Farr Inst Hlth Informat, London, England.
    Fairhurst-Hunter, Zammy
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Richard Doll Bldg,Old Rd Campus,Roosevelt Dr, Oxford OX3 7LF, England;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit CTSU, Richard Doll Bldg,Old Rd Campus,Roosevelt Dr, Oxford OX3 7LF, England.
    Hartwig, Fernando Pires
    Univ Fed Pelotas, Postgrad Program Epidemiol, Pelotas, RS, Brazil.
    Horta, Bernardo Lessa
    Univ Fed Pelotas, Postgrad Program Epidemiol, Pelotas, RS, Brazil.
    Hypponen, Elina
    Univ South Australia, Sansom Inst Hlth Res, Ctr Populat Hlth Res, Adelaide, SA, Australia;UCL GOS Inst Child Hlth, Populat Policy & Practice, London, England;South Australian Hlth & Med Res Inst, Adelaide, SA, Australia.
    Power, Christine
    UCL GOS Inst Child Hlth, Populat Policy & Practice, London, England.
    Moldovan, Max
    South Australian Hlth & Med Res Inst, Adelaide, SA, Australia.
    van Iperen, Erik
    Netherlands Heart Inst, Durrer Ctr Cardiovasc Res, Utrecht, Netherlands;Acad Med Ctr Amsterdam, Dept Clin Epidemiol Biostat & Bioinformat, Amsterdam, Netherlands.
    Hovingh, Kees
    Acad Med Ctr Amsterdam, Dept Vasc Med, Amsterdam, Netherlands.
    Demuth, Ilja
    Charite Univ Med Berlin, Berlin, Germany;Free Univ Berlin, Berlin, Germany;Humboldt Univ, Berlin, Germany;Berlin Inst Hlth, Lipid Clin, Interdisciplinary Metab Ctr, Berlin, Germany;Charite Univ Med Berlin, BCRT Berlin Inst Hlth, Ctr Regenerat Therapies, Berlin, Germany.
    Norman, Kristina
    Univ Potsdam, Inst Nutr Sci, D-14558 Nuthetal, Germany;Charite Univ Med Berlin, Geriatr Res Grp, D-13347 Berlin, Germany;German Inst Human Nutr Potsdam Rehbrucke, Dept Nutr & Gerontol, D-14558 Nuthetal, Germany.
    Steinhagen-Thiessen, Elisabeth
    Charite Univ Med Berlin, Berlin, Germany;Free Univ Berlin, Berlin, Germany;Humboldt Univ, Berlin, Germany;Berlin Inst Hlth, Lipid Clin, Interdisciplinary Metab Ctr, Berlin, Germany.
    Demuth, Juri
    ECA Econ GmbH, Berlin, Germany.
    Bertram, Lars
    Univ Lubeck, Lubeck Interdisciplinary Platform Genome Analyt L, Inst Neurogenet & Cardiogenet, Lubeck, Germany;Univ Oslo, Dept Psychol, Ctr Lifespan Changes Brain & Cognit LCBC, Oslo, Norway.
    Lill, Christina M.
    Univ Lubeck, Inst Neurogenet & Cardiogenet, Lubeck Interdisciplinary Platform Genome Analyt L, Genet & Mol Epidemiol Grp, Lubeck, Germany;Inst Human Genet, Lubeck, Germany;Imperial Coll, Sch Publ Hlth, Ageing Epidemiol Res Unit, London, England.
    Coassin, Stefan
    Med Univ Innsbruck, Dept Genet & Pharmacol, Inst Genet Epidemiol, A-6020 Innsbruck, Austria.
    Willeit, Johann
    Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria.
    Kiechl, Stefan
    Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria.
    Willeit, Karin
    Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria;Univ Bern, Univ Hosp Bern, Inselspital, Dept Neurol, Bern, Switzerland.
    Mason, Dan
    Bradford Royal Infirm, Bradford Inst Hlth Res, Bradford, W Yorkshire, England.
    Wright, John
    Bradford Royal Infirm, Bradford Inst Hlth Res, Bradford, W Yorkshire, England.
    Morris, Richard
    UCL, Dept Primary Care & Populat Hlth, London, England.
    Wanamethee, Goya
    UCL, Dept Primary Care & Populat Hlth, London, England.
    Whincup, Peter
    St Georges Univ London, Populat Hlth Res Inst, London, England.
    Ben-Shlomo, Yoav
    Univ Bristol, Populat Hlth Sci, Bristol, Avon, England.
    McLachlan, Stela
    Univ Edinburgh, Usher Inst, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland.
    Price, Jackie F.
    Univ Edinburgh, Usher Inst, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland.
    Kivimaki, Mika
    UCL, UCL Inst Epidemiol & Hlth Care, Dept Epidemiol & Publ Hlth, London, England.
    Welch, Catherine
    UCL, UCL Inst Epidemiol & Hlth Care, Dept Epidemiol & Publ Hlth, London, England.
    Sanchez-Galvez, Adelaida
    UCL, UCL Inst Epidemiol & Hlth Care, Dept Epidemiol & Publ Hlth, London, England.
    Marques-Vidal, Pedro
    Lausanne Univ Hosp, Dept Med, Internal Med, Lausanne, Switzerland.
    Nicolaides, Andrew
    Imperial Coll, Dept Vasc Surg, London, England;Univ Nicosia, Nicosia Med Sch, Dept Surg, Nicosia, Cyprus.
    Panayiotou, Andrie G.
    Cyprus Univ Technol, Cyprus Int Inst Environm & Publ Hlth, Limassol, Cyprus.
    Onland-Moret, N. Charlotte
    Univ Utrecht, Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
    van der Schouw, Yvonne T.
    Univ Utrecht, Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
    Matullo, Giuseppe
    IIGM, Turin, Italy;Univ Turin, Dept Med Sci, Turin, Italy.
    Fiorito, Giovanni
    IIGM, Turin, Italy;Univ Turin, Dept Med Sci, Turin, Italy.
    Guarrera, Simonetta
    IIGM, Turin, Italy;Univ Turin, Dept Med Sci, Turin, Italy.
    Sacerdote, Carlotta
    Citta Salute & Sci Univ Hosp, Unit Canc Epidemiol, Turin, Italy;Ctr Canc Prevent CPO, Turin, Italy.
    Wareham, Nicholas J.
    Univ Cambridge, Addenbrookes Hosp, Sch Clin Med, MRC Epidemiol Unit,Inst Metab Sci, Cambridge Biomed Campus, Cambridge, England.
    Langenberg, Claudia
    Univ Cambridge, Addenbrookes Hosp, Sch Clin Med, MRC Epidemiol Unit,Inst Metab Sci, Cambridge Biomed Campus, Cambridge, England.
    Scott, Robert A.
    Univ Cambridge, Addenbrookes Hosp, Sch Clin Med, MRC Epidemiol Unit,Inst Metab Sci, Cambridge Biomed Campus, Cambridge, England.
    Luan, Jian'an
    Univ Cambridge, Addenbrookes Hosp, Sch Clin Med, MRC Epidemiol Unit,Inst Metab Sci, Cambridge Biomed Campus, Cambridge, England.
    Bobak, Martin
    UCL, UCL Inst Epidemiol & Hlth Care, Dept Epidemiol & Publ Hlth, London, England.
    Malyutina, Sofia
    Novosibirsk State Med Univ, Novosibirsk, Russia;Russian Acad Med Sci, Siberian Branch, Inst Internal & Prevent Med, Novosibirsk, Russia.
    Pajak, Andrzej
    Jagiellonian Univ, Coll Med, Fac Hlth Sci, Dept Epidemiol & Populat Studies, Krakow, Poland.
    Kubinova, Ruzena
    Natl Inst Publ Hlth, Prague, Czech Republic.
    Tamosiunas, Abdonas
    Lithuanian Univ Hlth Sci, Kaunas, Lithuania.
    Pikhart, Hynek
    UCL, UCL Inst Epidemiol & Hlth Care, Dept Epidemiol & Publ Hlth, London, England.
    Grarup, Niels
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark.
    Pedersen, Oluf
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark.
    Hansen, Torben
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark.
    Linneberg, Allan
    Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark;Bispebjerg & Frederiksberg Hosp, Ctr Clin Res & Prevent, Copenhagen, Capital Region, Denmark.
    Jess, Tine
    Bispebjerg & Frederiksberg Hosp, Ctr Clin Res & Prevent, Copenhagen, Capital Region, Denmark.
    Cooper, Jackie
    UCL, Dept Med, Ctr Cardiovasc Genet, London, England.
    Humphries, Steve E.
    UCL, Dept Med, Ctr Cardiovasc Genet, London, England.
    Brilliant, Murray
    Marshfield Clin Res Inst, Ctr Human Genet, Marshfield, WI USA.
    Kitchner, Terrie
    Marshfield Clin Res Inst, Ctr Human Genet, Marshfield, WI USA.
    Hakonarson, Hakon
    Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
    Carrell, David S.
    Kaiser Permanente Washington Hlth Res Inst, Seattle, WA USA.
    McCarty, Catherine A.
    Univ Minnesota, Minneapolis, MN USA.
    Lester, Kirchner H.
    Geisinger, Danville, PA USA.
    Larson, Eric B.
    Kaiser Permanente Washington Hlth Res Inst, Seattle, WA USA.
    Crosslin, David R.
    Univ Washington Seattle, Dept Biomed Informat & Med Educ, Seattle, WA USA.
    de Andrade, Mariza
    Mayo Clin, Rochester, MN USA.
    Roden, Dan M.
    Vanderbilt Univ, Sch Med, Dept Med, Dept Pharmacol,Dept Biomed Informat, Nashville, TN 37212 USA.
    Denny, Joshua C.
    Vanderbilt Univ, 221 Kirkland Hall, Nashville, TN 37235 USA.
    Carty, Cara
    WHI, Seattle, WA USA.
    Hancock, Stephen
    Univ Newcastle, Newcastle, NSW, Australia.
    Attia, John
    Univ Newcastle, Newcastle, NSW, Australia;Hunter Med Res Inst, Publ Hlth Program, Newcastle, NSW, Australia.
    Holliday, Elizabeth
    Univ Newcastle, Newcastle, NSW, Australia;Hunter Med Res Inst, Publ Hlth Program, Newcastle, NSW, Australia.
    Scott, Rodney
    Univ Newcastle, Newcastle, NSW, Australia.
    Schofield, Peter
    Hunter New England Local Hlth Dist, Newcastle, NSW, Australia.
    O'Donnell, Martin
    Populat Hlth Res Inst, Hamilton, ON, Canada.
    Yusuf, Salim
    Populat Hlth Res Inst, Hamilton, ON, Canada.
    Chong, Michael
    Populat Hlth Res Inst, Hamilton, ON, Canada.
    Pare, Guillaume
    Populat Hlth Res Inst, Hamilton, ON, Canada.
    van der Harst, Pim
    Netherlands Heart Inst, Durrer Ctr Cardiovasc Res, Utrecht, Netherlands;Acad Med Ctr Amsterdam, Dept Clin Epidemiol Biostat & Bioinformat, Amsterdam, Netherlands;Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands;Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
    Said, M. Abdullah
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
    Eppinga, Ruben N.
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
    Verweij, Niek
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
    Snieder, Harold
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.
    Christen, Tim
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands.
    Mook-Kanamori, D. O.
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands.
    Gustafsson, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Lind, Lars
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA;.
    Ingelsson, Erik
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA.
    Pazoki, Raha
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands;Imperial Coll London, Dept Epidemiol & Biostat, London, England.
    Franco, Oscar
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    Hofman, Albert
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    Uitterlinden, Andre
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    Dehghan, Abbas
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    Teumer, Alexander
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany.
    Baumeister, Sebastian
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany;Ludwig Maximilians Univ Munchen, Chair Epidemiol, UNIKA T Augsburg, Augsburg, Germany.
    Doerr, Marcus
    DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany;Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany.
    Lerch, Markus M.
    Univ Med Greifswald, Dept Internal Med A, Greifswald, Germany.
    Voelker, Uwe
    DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany;Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany.
    Voelzke, Henry
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany.
    Ward, Joey
    Univ Glasgow, Inst Hlth & Wellbeing, Glasgow G12 8RZ, Lanark, Scotland.
    Pell, Jill P.
    Univ Glasgow, Inst Hlth & Wellbeing, Glasgow G12 8RZ, Lanark, Scotland.
    Meade, Tom
    London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, London, England.
    Christophersen, Ingrid E.
    Vestre Viken Hosp Trust, Baerum Hosp, Dept Med Res, Gjettum, Norway.
    Maitland-van der Zee, Anke H.
    Univ Utrecht, Fac Sci, Utrecht Inst Pharmaceut Sci, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht, Netherlands;Univ Amsterdam, Acad Med Ctr, Dept Resp Med, Amsterdam, Netherlands.
    Baranova, Ekaterina V.
    Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.
    Young, Robin
    Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.
    Ford, Ian
    Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.
    Campbell, Archie
    Univ Edinburgh, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.
    Padmanabhan, Sandosh
    Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow G12 8TA, Lanark, Scotland.
    Bots, Michiel L.
    Cyprus Univ Technol, Cyprus Int Inst Environm & Publ Hlth, Limassol, Cyprus.
    Grobbee, Diederick E.
    Cyprus Univ Technol, Cyprus Int Inst Environm & Publ Hlth, Limassol, Cyprus.
    Froguel, Philippe
    Univ Lille, Inst Pasteur Lille, CNRS, UMR 8199,EGID, F-59000 Lille, France;Imperial Coll London, Dept Genom Common Dis, London W12 0NN, England.
    Thuillier, Dorothee
    Univ Lille, Inst Pasteur Lille, CNRS, UMR 8199,EGID, F-59000 Lille, France.
    Roussel, Ronan
    INSERM, Ctr Rech Cordeliers, U1138, Paris, France;Univ Paris Diderot, Sorbonne Paris Cite, UFR Med, Paris, France;Hop Bicha, AP HP, Dept Diabetol Endocrinol & Nutr, Paris, France.
    Bonnefond, Amelie
    Univ Lille, Inst Pasteur Lille, CNRS, UMR 8199,EGID, F-59000 Lille, France.
    Cariou, Bertrand
    Univ Nantes, CHU Nantes, CNRS, Inst Thorax,INSERM, Nantes, France.
    Smart, Melissa
    Univ Essex, Inst Social & Econ Res, Colchester, Essex, England.
    Bao, Yanchun
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
    Kumari, Meena
    Boston Univ, Sch Med, Boston, MA 02118 USA.
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
    Hopewell, Jemma C.
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Richard Doll Bldg,Old Rd Campus,Roosevelt Dr, Oxford OX3 7LF, England;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit CTSU, Richard Doll Bldg,Old Rd Campus,Roosevelt Dr, Oxford OX3 7LF, England.
    Seshadri, Sudha
    Boston Univ, Sch Med, Boston, MA 02118 USA.
    Dale, Caroline
    UCL, Farr Inst Hlth Informat, London, England.
    Costa, Rui Providencia E.
    UCL, Farr Inst Hlth Informat, London, England.
    Ridker, Paul M.
    Harvard Med Sch, Ctr Cardiovasc Dis Prevent, Brigham & Womens Hosp, Boston, MA 02115 USA.
    Chasman, Daniel I.
    Harvard Med Sch, Ctr Cardiovasc Dis Prevent, Brigham & Womens Hosp, Boston, MA 02115 USA.
    Reiner, Alex P.
    UWash, Seattle, WA USA.
    Ritchie, Marylyn D.
    Penn State, State Coll, PA USA.
    Lange, Leslie A.
    Univ Colorado Denver, Denver, CO USA.
    Cornish, Alex J.
    Inst Canc Res, Div Genet & Epidemiol, London, England.
    Dobbins, Sara E.
    Inst Canc Res, Div Genet & Epidemiol, London, England.
    Hemminki, Kari
    German Canc Res Ctr, Div Mol Genet Epidemiol, Neuenheimer Feld 580, D-69120 Heidelberg, Germany;Deutsch Krebsforschungszentrum, Heidelberg, Germany.
    Kinnersley, Ben
    Inst Canc Res, Div Genet & Epidemiol, London, England.
    Sanson, Marc
    Inst Cerveau Moelle Epiniere ICM, Paris, France;UPMC Univ Paris 06, Sorbonne Univ, UMR S 1127, F-75013 Paris, France.
    Labreche, Karim
    Inst Cerveau Moelle Epiniere ICM, Paris, France;UPMC Univ Paris 06, Sorbonne Univ, UMR S 1127, F-75013 Paris, France.
    Simon, Matthias
    Bethel Clin, Dept Neurosurg, Kantensiek 11, D-33617 Bielefeld, Germany.
    Bondy, Melissa
    Baylor Coll Med, Dan L Duncan Canc Ctr, Dept Pediat, Div Hematol Oncol, Houston, TX 77030 USA.
    Law, Philip
    Inst Canc Res, Div Genet & Epidemiol, London, England.
    Speedy, Helen
    Inst Canc Res, Div Genet & Epidemiol, London, England.
    Allan, James
    Newcastle Univ, Northern Inst Canc Res, Newcastle Upon Tyne, Tyne & Wear, England.
    Li, Ni
    Inst Canc Res, Div Genet & Epidemiol, London, England.
    Went, Molly
    Inst Canc Res, Div Genet & Epidemiol, London, England.
    Weinhold, Niels
    Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA.
    Morgan, Gareth
    Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA.
    Sonneveld, Pieter
    Erasmus MC Canc Inst, Dept Hematol, NL-3075 EA Rotterdam, Netherlands.
    Nilsson, Bjorn
    Dept Lab Med, Hematol & Transfus Med, BMC B13, SE-22184 Lund, Sweden.
    Goldschmidt, Hartmut
    Univ Clin Heidelberg, Internal Med 5, Heidelberg, Germany;Natl Ctr Tumor Dis NCT, Heidelberg, Germany.
    Sud, Amit
    Inst Canc Res, Div Genet & Epidemiol, London, England.
    Engert, Andreas
    Univ Hosp Cologne, Dept Internal Med, Cologne, Germany.
    Hansson, Markus
    Skane Univ Hosp, Hematol Clin, Skane, Sweden;Lund Univ, Wallenberg Ctr Mol Med, Lund, Sweden.
    Hemingway, Harry
    UCLs BHF Res Accelerator Ctr, London, England;UCL, Hlth Data Res UK, 222 Euston Rd, London NW1 2DA, England;UCL, Inst Hlth Informat, 222 Euston Rd, London NW1 2DA, England;UCL, Univ Coll London Hosp, Biomed Res Ctr, Natl Inst Hlth Res, 222 Euston Rd, London NW1 2DA, England.
    Asselbergs, Folkert W.
    UCL, Inst Cardiovasc Sci, 222 Euston Rd, London NW1 2DA, England;Univ Utrecht, Univ Med Ctr Utrecht, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands;UCLs BHF Res Accelerator Ctr, London, England;UCL, Hlth Data Res UK, London, England;UCL, Inst Hlth Informat, London, England.
    Patel, Riyaz S.
    UCL, Inst Cardiovasc Sci, 222 Euston Rd, London NW1 2DA, England;UCLs BHF Res Accelerator Ctr, London, England;St Bartholomews Hosp, Barts Heart Ctr, London, England.
    Keating, Brendan J.
    Univ Penn, Philadelphia, PA 19104 USA.
    Sattar, Naveed
    Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow G12 8TA, Lanark, Scotland.
    Houlston, Richard
    Inst Canc Res, Div Genet & Epidemiol, London, England.
    Casas, Juan P.
    Vet Affairs Boston Healthcare Syst, Massachusetts Vet Epidemiol & Res Informat Ctr MA, Boston, MA USA.
    Hingorani, Aroon D.
    UCL, Inst Cardiovasc Sci, 222 Euston Rd, London NW1 2DA, England;UCLs BHF Res Accelerator Ctr, London, England.
    Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK92019Inngår i: BMC Cardiovascular Disorders, ISSN 1471-2261, E-ISSN 1471-2261, Vol. 19, nr 1, artikkel-id 240Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Methods: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. Results: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable. Conclusions: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.

  • 262.
    Schmidt, Amand F.
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    UCL, Inst Cardiovasc Sci, London NW1 2DA, England.;UCL, UCL Inst Hlth Informat, Farr Inst Hlth Informat Res, London, England..
    Swerdlow, Daniel I.
    UCL, Inst Cardiovasc Sci, London NW1 2DA, England.;Imperial Coll London, Dept Med, Fac Med, London, England..
    Holmes, Michael V.
    Univ Oxford, Clin Trial Serv Unit, Nuffield Dept Populat Hlth, Oxford, England.;Univ Oxford, Epidemiol Studies Unit CTSU, Nuffield Dept Populat Hlth, Oxford, England.;Univ Oxford, Med Res Council, Populat Hlth Res Unit, Oxford, England..
    Patel, Riyaz S.
    UCL, Inst Cardiovasc Sci, London NW1 2DA, England.;UCL, UCL Inst Hlth Informat, Farr Inst Hlth Informat Res, London, England.;St Bartholomews Hosp, Barts Heart Ctr, London, England..
    Fairhurst-Hunter, Zammy
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Lyall, Donald M.
    Univ Glasgow, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland..
    Hartwig, Fernando Pires
    Univ Fed Pelotas, Postgrad Program Epidemiol, Pelotas, Brazil..
    Horta, Bernardo Lessa
    Univ Fed Pelotas, Postgrad Program Epidemiol, Pelotas, Brazil..
    Hypponen, Elina
    Univ South Australia, Ctr Populat Hlth Res, Sansom Inst Hlth Res, Adelaide, SA, Australia.;UCL Great Ormond St Inst Child Hlth, Populat Policy & Practice, London, England.;South Australian Hlth & Med Res Inst, Adelaide, SA, Australia..
    Power, Christine
    UCL Great Ormond St Inst Child Hlth, Populat Policy & Practice, London, England..
    Moldovan, Max
    Univ South Australia, Sch Hlth Sci, Adelaide, SA, Australia.;EMBL Australia, South Australian Hlth & Med Res Inst, Adelaide, SA, Australia..
    van Iperen, Erik
    Netherlands Heart Inst, Durrer Ctr Cardiovasc Res, Utrecht, Netherlands.;Acad Med Ctr, Dept Clin Epidemiol Biostat & Bioinformat, Amsterdam, Netherlands..
    Hovingh, G. Kees
    Acad Med Ctr, Dept Vasc Med, Amsterdam, Netherlands..
    Demuth, Ilja
    Charite Univ Med Berlin, Charite Res Grp Geriatr, Berlin, Germany.;Charite Univ Med Berlin, Inst Med & Human Genet, Berlin, Germany..
    Norman, Kristina
    Charite Univ Med Berlin, Charite Res Grp Geriatr, Berlin, Germany..
    Steinhagen-Thiessen, Elisabeth
    Charite Univ Med Berlin, Charite Res Grp Geriatr, Berlin, Germany..
    Demuth, Juri
    E CA Econ GmbH, Berlin, Germany..
    Bertram, Lars
    Imperial Coll London, Neuroepidemiol & Ageing Res Unit, Fac Med, London, England.;Univ Lubeck, Lubeck Interdisciplinary Platform Genome Analyt L, Inst Neurogenet, Lubeck, Germany.;Univ Lubeck, Lubeck Interdisciplinary Platform Genome Analyt L, Inst Integrat & Expt Genom, Lubeck, Germany..
    Liu, Tian
    Max Planck Inst Human Dev, Berlin, Germany.;Max Planck Inst Mol Genet, Berlin, Germany..
    Coassin, Stefan
    Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol Innsbruck, Innsbruck, Austria..
    Willeit, Johann
    Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria..
    Kiechl, Stefan
    Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria..
    Willeit, Karin
    Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria..
    Mason, Dan
    Bradford Royal Infirm, Bradford Inst Hlth Res, Bradford, W Yorkshire, England..
    Wright, John
    Bradford Royal Infirm, Bradford Inst Hlth Res, Bradford, W Yorkshire, England..
    Morris, Richard
    Univ Bristol, Sch Social & Community Med, Bristol, Avon, England..
    Wanamethee, Goya
    UCL, Dept Primary Care & Populat Hlth, London, England..
    Whincup, Peter
    St Georges Univ London, Populat Hlth Res Inst, London, England..
    Ben-Shlomo, Yoav
    Univ Bristol, Sch Social & Community Med, Bristol, Avon, England..
    McLachlan, Stela
    Univ Edinburgh, Ctr Populat Hlth Sci, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland..
    Price, Jackie F.
    Univ Edinburgh, Ctr Populat Hlth Sci, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland..
    Kivimaki, Mika
    UCL, UCL Inst Epidemiol & Hlth Care, Dept Epidemiol & Publ Hlth, London, England..
    Welch, Catherine
    UCL, UCL Inst Epidemiol & Hlth Care, Dept Epidemiol & Publ Hlth, London, England..
    Sanchez-Galvez, Adelaida
    UCL, UCL Inst Epidemiol & Hlth Care, Dept Epidemiol & Publ Hlth, London, England..
    Marques-Vidal, Pedro
    Univ Lausanne Hosp, Dept Med, Internal Med Unit, Lausanne, Switzerland..
    Nicolaides, Andrew
    Imperial Coll London, Dept Vasc Surg, Fac Med, London, England.;Univ Nicosia, Nicosia Med Sch, Dept Surg, Nicosia, Cyprus..
    Panayiotou, Andrie G.
    Cyprus Univ Technol, Cyprus Int Inst Environm & Publ Hlth, Limassol, Cyprus..
    Onland-Moret, N. Charlotte
    Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands..
    van der Schouw, Yvonne T.
    Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands..
    Matullo, Giuseppe
    Human Genet Fdn, Turin, Italy.;Univ Turin, Dept Med Sci, Turin, Italy..
    Fiorito, Giovanni
    Human Genet Fdn, Turin, Italy.;Univ Turin, Dept Med Sci, Turin, Italy..
    Guarrera, Simonetta
    Human Genet Fdn, Turin, Italy.;Univ Turin, Dept Med Sci, Turin, Italy..
    Sacerdote, Carlotta
    San Giovanni Battista Hosp, Canc Epidemiol Unit, Turin, Italy.;CPO Piemonte, Ctr Oncol Prevent, Turin, Italy..
    Wareham, Nicholas J.
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Inst Metab Sci, Cambridge, England..
    Langenberg, Claudia
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Inst Metab Sci, Cambridge, England..
    Scott, Robert
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Inst Metab Sci, Cambridge, England..
    Luan, Jian'an
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Inst Metab Sci, Cambridge, England..
    Bobak, Martin
    UCL, UCL Inst Epidemiol & Hlth Care, Dept Epidemiol & Publ Hlth, London, England..
    Malyutina, Sofi A.
    Novosibirsk State Med Univ, Novosibirsk, Russia.;Russian Acad Med Sci, Inst Internal & Prevent Med, Siberian Branch, Novosibirsk, Russia..
    Pajak, Andrzej
    Jagiellonian Univ, Coll Med, Krakow, Poland..
    Kubinova, Ruzena
    Natl Inst Publ Hlth, Prague, Czech Republic..
    Tamosiunas, Abdonas
    Lithuanian Univ Hlth Sci, Kaunas, Lithuania..
    Pikhart, Hynek
    UCL, UCL Inst Epidemiol & Hlth Care, Dept Epidemiol & Publ Hlth, London, England..
    Husemoen, Lise Lotte Nystrup
    Capital Reg Denmark, Res Ctr Prevent & Hlth, Copenhagen, Denmark..
    Grarup, Niels
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark..
    Pedersen, Oluf
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark..
    Hansen, Torben
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark..
    Linneberg, Allan
    Capital Reg Denmark, Res Ctr Prevent & Hlth, Copenhagen, Denmark.;Rigshosp, Dept Clin Expt Res, Copenhagen, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark..
    Simonsen, Kenneth Starup
    Capital Reg Denmark, Res Ctr Prevent & Hlth, Copenhagen, Denmark..
    Cooper, Jackie
    UCL, Ctr Cardiovasc Genet, London, England..
    Humphries, Steve E.
    UCL, Ctr Cardiovasc Genet, London, England..
    Brilliant, Murray
    Marshfield Clin Res Fdn, Ctr Human Genet, Marshfield, WI USA..
    Kitchner, Terrie
    Marshfield Clin Res Fdn, Ctr Human Genet, Marshfield, WI USA..
    Hakonarson, Hakon
    Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA..
    Carrell, David S.
    Grp Hlth Res Inst, Seattle, WA USA..
    McCarty, Catherine A.
    Essentia Inst Rural Hlth, Duluth, MN USA..
    Kirchner, H. Lester
    Geisinger Med Clin, Ctr Hlth Res, Danville, PA USA..
    Larson, Eric B.
    Grp Hlth Res Inst, Seattle, WA USA..
    Crosslin, David R.
    Grp Hlth Res Inst, Seattle, WA USA..
    de Andrade, Mariza
    Mayo Clin, Div Biomed Stat & Informat, Rochester, MN USA..
    Roden, Dan M.
    Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA.;Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37212 USA..
    Denny, Joshua C.
    Vanderbilt Univ, Sch Med, Dept Biomed Informat, Nashville, TN 37212 USA..
    Carty, Cara
    George Washington Univ, Washington, DC USA..
    Hancock, Stephen
    Univ Newcastle, Newcastle, NSW, Australia..
    Attia, John
    Univ Newcastle, Newcastle, NSW, Australia..
    Holliday, Elizabeth
    Univ Newcastle, Newcastle, NSW, Australia..
    Donnell, Martin O'
    Populat Hlth Res Inst, Hamilton, ON, Canada..
    Yusuf, Salim
    Populat Hlth Res Inst, Hamilton, ON, Canada..
    Chong, Michael
    Populat Hlth Res Inst, Hamilton, ON, Canada..
    Pare, Guillaume
    Populat Hlth Res Inst, Hamilton, ON, Canada..
    van der Harst, Pim
    Netherlands Heart Inst, Durrer Ctr Cardiovasc Res, Utrecht, Netherlands.;Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.;Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands..
    Said, M. Abdullah
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands..
    Eppinga, Ruben N.
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands..
    Verweij, Niek
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands..
    Snieder, Harold
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands..
    Christen, Tim
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands..
    Mook-Kanamori, Dennis O.
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands..
    Gustafsson, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA..
    Pazoki, Raha
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Franco, Oscar
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Hofman, Albert
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Uitterlinden, Andre
    Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands..
    Dehghan, Abbas
    Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, Dept Biostat & Epidemiol, London, England.;Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Teumer, Alexander
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany.;German Ctr Cardiovasc Res DZHK, Greifswald, Germany..
    Baumeister, Sebastian
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany.;Univ Regensburg, Dept Epidemiol & Prevent Med, Regensburg, Germany..
    Doerr, Marcus
    Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany.;German Ctr Cardiovasc Res DZHK, Greifswald, Germany..
    Lerch, Markus M.
    Univ Med Greifswald, Dept Med A, Greifswald, Germany..
    Voelker, Uwe
    Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany.;German Ctr Cardiovasc Res DZHK, Greifswald, Germany..
    Voelzke, Henry
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany.;German Ctr Cardiovasc Res DZHK, Greifswald, Germany..
    Ward, Joey
    Univ Glasgow, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland..
    Pell, Jill P.
    Univ Glasgow, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland..
    Smith, Daniel J.
    Univ Glasgow, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland..
    Meade, Tom
    London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, London, England..
    Maitland-van der Zee, Anke H.
    Acad Med Ctr, Dept Resp Med, Amsterdam, Netherlands.;Univ Utrecht, Fac Sci, Utrecht Inst Pharmaceut Sci, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht, Netherlands..
    Baranova, Ekaterina V.
    Univ Utrecht, Fac Sci, Utrecht Inst Pharmaceut Sci, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht, Netherlands..
    Young, Robin
    Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland..
    Ford, Ian
    Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland..
    Campbell, Archie
    Univ Edinburgh, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland..
    Padmanabhan, Sandosh
    Univ Glasgow, Cardiovasc & Med Sci, Glasgow, Lanark, Scotland..
    Bots, Michiel L.
    Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands..
    Grobbee, Diederick E.
    Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands..
    Froguel, Philippe
    Imperial Coll London, Fac Med, Dept Genom Common Dis, London, England.;Univ Lille, Inst Pasteur Lille, EGID, CNRS,UMR 8199, Lille, France..
    Thuillier, Dorothee
    Univ Lille, Inst Pasteur Lille, EGID, CNRS,UMR 8199, Lille, France..
    Balkau, Beverley
    INSERM, U1018, Ctr Rech Epidemiol & Sante Populat CESP, Renal & Cardiovasc Epidemiol, Villejuif, France..
    Bonnefond, Amelie
    Imperial Coll London, Fac Med, Dept Genom Common Dis, London, England.;Univ Lille, Inst Pasteur Lille, EGID, CNRS,UMR 8199, Lille, France..
    Cariou, Bertrand
    Univ Nantes, CHU Nantes, Inst Thorax, INSERM,CNRS, Nantes, France..
    Smart, Melissa
    Univ Essex, Inst Social & Econ Res, Colchester, Essex, England..
    Bao, Yanchun
    Univ Essex, Inst Social & Econ Res, Colchester, Essex, England..
    Kumari, Meena
    Univ Essex, Inst Social & Econ Res, Colchester, Essex, England..
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Ridker, Paul M.
    Harvard Med Sch, Brigham & Womens Hosp, Ctr Cardiovasc Dis Prevent, Boston, MA USA..
    Chasman, Daniel I.
    Harvard Med Sch, Brigham & Womens Hosp, Ctr Cardiovasc Dis Prevent, Boston, MA USA..
    Reiner, Alex P.
    Univ Washington, Fred Hutchinson Canc Res Ctr, Dept Epidemiol, Seattle, WA 98195 USA..
    Lange, Leslie A.
    Univ Colorado, Anschutz Med Campus, Denver, CO 80202 USA..
    Ritchie, Marylyn D.
    Geisinger Hlth Syst, Biomed & Translat Informat, Danville, PA USA.;Penn State Univ, Huck Inst Life Sci, Dept Biochem & Mol Biol, University Pk, PA 16802 USA..
    Asselbergs, Folkert W.
    UCL, Inst Cardiovasc Sci, London NW1 2DA, England.;UCL, UCL Inst Hlth Informat, Farr Inst Hlth Informat Res, London, England.;Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.;Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Utrecht, Netherlands..
    Casas, Juan-Pablo
    UCL, UCL Inst Hlth Informat, Farr Inst Hlth Informat Res, London, England..
    Keating, Brendan J.
    Univ Penn, Dept Surg, Philadelphia, PA 19104 USA..
    Preiss, David
    Univ Oxford, Clin Trial Serv Unit, Nuffield Dept Populat Hlth, Oxford, England.;Univ Oxford, Epidemiol Studies Unit CTSU, Nuffield Dept Populat Hlth, Oxford, England.;Univ Oxford, Med Res Council, Populat Hlth Res Unit, Oxford, England..
    Hingorani, Aroon D.
    UCL, Inst Cardiovasc Sci, London NW1 2DA, England.;UCL, UCL Inst Hlth Informat, Farr Inst Hlth Informat Res, London, England..
    Sattar, Naveed
    Univ Glasgow, Cardiovasc & Med Sci, Glasgow, Lanark, Scotland..
    PCSK9 genetic variants and risk of type 2 diabetes: a mendelian randomisation study2017Inngår i: The Lancet Diabetes and Endocrinology, ISSN 2213-8587, E-ISSN 2213-8595, Vol. 5, nr 2, s. 97-105Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way off sets their substantial benefi ts. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely eff ects of PCSK9 inhibitors on diabetes risk. Methods In this mendelian randomisation study, we used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA 1c, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using a standardised analysis plan, meta-analyses, and weighted gene-centric scores. Findings Data were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL cholesterol showed associations with increased fasting glucose (0.09 mmol/L, 95% CI 0.02 to 0.15), bodyweight (1.03 kg, 0.24 to 1.82), waist-to-hip ratio (0.006, 0.003 to 0.010), and an odds ratio for type diabetes of 1.29 (1.11 to 1.50). Based on the collected data, we did not identify associations with HbA 1c (0.03%, -0.01 to 0.08), fasting insulin (0.00%, -0.06 to 0.07), and BMI (0.11 kg/m(2), -0.09 to 0.30). Interpretation PCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, bodyweight, and waist-to-hip ratio, and an increased risk of type 2 diabetes. In trials of PCSK9 inhibitor drugs, investigators should carefully assess these safety outcomes and quantify the risks and benefi ts of PCSK9 inhibitor treatment, as was previously done for statins.

  • 263. Scott, R. A.
    et al.
    Pasko, D.
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Yaghootkar, H.
    Barker, A.
    Sharp, S. J.
    Walker, M.
    Wareham, N. J.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Frayling, T.
    Langenberg, C.
    A genetic risk score comprising common variants associated with fasting insulin is associated with OGTT- and clamp-based indices of whole body insulin sensitivity2013Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 56, s. S144-S145Artikkel i tidsskrift (Annet vitenskapelig)
  • 264. Scott, Robert A
    et al.
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Pasko, Dorota
    Barker, Adam
    Sharp, Stephen J
    Arriola, Larraitz
    Balkau, Beverley
    Barricarte, Aurelio
    Barroso, Inês
    Boeing, Heiner
    Clavel-Chapelon, Françoise
    Crowe, Francesca L
    Dekker, Jacqueline M
    Fagherazzi, Guy
    Ferrannini, Ele
    Forouhi, Nita G
    Franks, Paul W
    Gavrila, Diana
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Grioni, Sara
    Groop, Leif C
    Kaaks, Rudolf
    Key, Timothy J
    Kühn, Tilman
    Lotta, Luca A
    Nilsson, Peter M
    Overvad, Kim
    Palli, Domenico
    Panico, Salvatore
    Quirós, J Ramón
    Rolandsson, Olov
    Roswall, Nina
    Sacerdote, Carlotta
    Sala, Núria
    Sánchez, María-José
    Schulze, Matthias B
    Siddiq, Afshan
    Slimani, Nadia
    Sluijs, Ivonne
    Spijkerman, Annemieke Mw
    Tjonneland, Anne
    Tumino, Rosario
    van der A, Daphne L
    Yaghootkar, Hanieh
    McCarthy, Mark I
    Semple, Robert K
    Riboli, Elio
    Walker, Mark
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Frayling, Tim M
    Savage, David B
    Langenberg, Claudia
    Wareham, Nicholas J
    Common genetic variants highlight the role of insulin resistance and body fat distribution in type 2 diabetes, independently of obesity2014Inngår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 63, nr 12, s. 4378-4387Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We aimed to validate genetic variants as instruments for insulin resistance and secretion, to characterise their association with intermediate phenotypes, and to investigate their role in T2D risk among normal-weight, overweight and obese individuals.We investigated the association of genetic scores with euglycaemic-hyperinsulinaemic clamp- and OGTT-based measures of insulin resistance and secretion, and a range of metabolic measures in up to 18,565 individuals. We also studied their association with T2D risk among normal-weight, overweight and obese individuals in up to 8,124 incident T2D cases. The insulin resistance score was associated with lower insulin sensitivity measured by M/I value (β in SDs-per-allele [95%CI]:-0.03[-0.04,-0.01];p=0.004). This score was associated with lower BMI (-0.01[-0.01,-0.0;p=0.02) and gluteofemoral fat-mass (-0.03[-0.05,-0.02;p=1.4x10-6), and with higher ALT (0.02[0.01,0.03];p=0.002) and gamma-GT (0.02[0.01,0.03];p=0.001). While the secretion score had a stronger association with T2D in leaner individuals (pinteraction=0.001), we saw no difference in the association of the insulin resistance score with T2D among BMI- or waist-strata(pinteraction>0.31). While insulin resistance is often considered secondary to obesity, the association of the insulin resistance score with lower BMI and adiposity and with incident T2D even among individuals of normal weight highlights the role of insulin resistance and ectopic fat distribution in T2D, independently of body size.

  • 265.
    Scott, Robert A.
    et al.
    Univ Cambridge, Sch Clin Med, MRC, Epidemiol Unit,Inst Metab Sci, Cambridge Biomedical Campus, Cambridge CB2 0QQ, England..
    Freitag, Daniel F.
    Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England.;Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England..
    Li, Li
    GlaxoSmithKline, Stat Genet Projects Clin Platforms & Sci PCPS, Res Triangle Pk, NC 27709 USA..
    Chu, Audrey Y.
    Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA..
    Surendran, Praveen
    Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England..
    Young, Robin
    Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England..
    Grarup, Niels
    Univ Copenhagen, NovoNordisk Fdn, Fac Hlth & Med Sci, Ctr Basic Metab Res, DK-2200 Copenhagen, Denmark..
    Stancakova, Alena
    Univ Eastern Finland, Inst Clin Med, Internal Med, FI-70211 Kuopio, Finland..
    Chen, Yuning
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA..
    Varga, Tibor V.
    Lund Univ, Genet & Mol Epidemiol Unit, Dept Clin Sci, SE-205 Malmo, Sweden..
    Yaghootkar, Hanieh
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter EX1 2LU, Devon, England..
    Luan, Jian'an
    Univ Cambridge, Sch Clin Med, MRC, Epidemiol Unit,Inst Metab Sci, Cambridge Biomedical Campus, Cambridge CB2 0QQ, England..
    Zhao, Jing Hua
    Univ Cambridge, Sch Clin Med, MRC, Epidemiol Unit,Inst Metab Sci, Cambridge Biomedical Campus, Cambridge CB2 0QQ, England..
    Willems, Sara M.
    Univ Cambridge, Sch Clin Med, MRC, Epidemiol Unit,Inst Metab Sci, Cambridge Biomedical Campus, Cambridge CB2 0QQ, England.;Erasmus Univ, Med Ctr, Dept Epidemiol, Genet Epidemiol Unit, NL-3000 CE Rotterdam, Netherlands..
    Wessel, Jennifer
    Fairbanks Sch Publ Hlth, Dept Epidemiol, Indianapolis, IN 46202 USA.;Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA..
    Wang, Shuai
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA..
    Maruthur, Nisa
    Johns Hopkins Univ, Sch Med, Div Gen Internal Med, Baltimore, MD 21205 USA.;Johns Hopkins Univ, Welch Ctr Prevent Epidemol & Clin Res, Baltimore, MD 21205 USA.;Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA..
    Michailidou, Kyriaki
    Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Strangeways Lab, Cambridge CB1 8RN, England..
    Pirie, Ailith
    Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Strangeways Lab, Cambridge CB1 8RN, England..
    van der Lee, Sven J.
    Erasmus Univ, Dept Epidemiol, Med Ctr, NL-3000 CA Rotterdam, Netherlands..
    Gillson, Christopher
    Univ Cambridge, Sch Clin Med, MRC, Epidemiol Unit,Inst Metab Sci, Cambridge Biomedical Campus, Cambridge CB2 0QQ, England..
    Al Olama, Ali Amin
    Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Strangeways Lab, Cambridge CB1 8RN, England..
    Amouyel, Philippe
    Univ Lille, Ctr Hosp Reg Univ Lille, INSERM, Inst Pasteur Lille,UMR 1167,RID AGE, F-59000 Lille, France..
    Arriola, Larraitz
    Publ Hlth Div Gipuzkoa, San Sebastian 20013, Spain.;Basque Govt, Inst BIOdonostia, San Sebastian 20014, Spain.;CIBER Epidemiol & Salud Publ CIBERESP, Madrid 28029, Spain..
    Arveiler, Dominique
    Univ Strasbourg, Dept Epidemiol & Publ Hlth EA3430, F-67085 Strasbourg, France..
    Aviles-Olmos, Iciar
    UCL Inst Neurol, Sobell Partment Motor Neurosci, London WC1N 3BG, England..
    Balkau, Beverley
    INSERM, Ctr Rech Epidemiol & Sante Populat CESP, F-94807 Villejuif, France.;Univ Paris 11, F-94805 Villejuif, France..
    Barricarte, Aurelio
    CIBER Epidemiol & Salud Publ CIBERESP, Madrid 28029, Spain.;Navarre Publ Hlth Inst ISPN, Pamplona 31003, Spain..
    Barroso, Ines
    Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.;Univ Paris 11, F-94805 Villejuif, France..
    Garcia, Sara Benlloch
    Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Strangeways Lab, Cambridge CB1 8RN, England..
    Bis, Joshua C.
    Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98101 USA..
    Blankenberg, Stefan
    Univ Heart Ctr Hamburg, Dept Gen & Intervent Cardiol, D-20246 Hamburg, Germany..
    Boehnke, Michael
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Boeing, Heiner
    German Inst Human Nutr, Potsdam Rehbruecke, D-14558 Nuthetal, Germany..
    Boerwinkle, Eric
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX 77025 USA.;Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA..
    Borecki, Ingrid B.
    Washington Univ, Sch Med, Div Stat Genom, Dept Genet, St Louis, MO 63108 USA..
    Bork-Jensen, Jette
    Univ Copenhagen, NovoNordisk Fdn, Fac Hlth & Med Sci, Ctr Basic Metab Res, DK-2200 Copenhagen, Denmark..
    Bowden, Sarah
    Univ Birmingham, Inst Canc Studies, Canc Res UK Clin Trials Unit, Birmingham B15 2TT, W Midlands, England..
    Caldas, Carlos
    Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge CB2 0RE, England.;Univ Cambridge, Li Ka Shing Ctr, Dept Oncol, Cambridge CB2 0RE, England..
    Caslake, Muriel
    Univ Glasgow, Glasgow G12 8QQ, Lanark, Scotland..
    Cupples, L. Adrienne
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.;NHLBI, Framingham Heart Study, Framingham, MA 01702 USA..
    Cruchaga, Carlos
    Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA..
    Czajkowski, Jacek
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63108 USA.;Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63108 USA..
    den Hoed, Marcel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Dunn, Janet A.
    Univ Warwick, Warwick Clin Trials Unit, Gibbet Hill Rd, Coventry CV4 7AL, W Midlands, England..
    Earl, Helena M.
    Univ Cambridge, Cambridge CB2 0QQ, England.;Cambridge Univ Hosp Natl Hlth Serv Fdn Trust, Natl Inst Hlth Res, Cambridge Biomed Res Ctr, Cambridge CB2 0QQ, England..
    Ehret, Georg B.
    Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA..
    Ferrannini, Ele
    CNR, Inst Clin Physiol, I-56124 Pisa, Italy..
    Ferrieres, Jean
    Ctr Hosp Univ CHU Toulouse, Dept Epidemiol, INSERM, UMR 1027, F-31000 Toulouse, France..
    Foltynie, Thomas
    UCL Inst Neurol, Sobell Partment Motor Neurosci, London WC1N 3BG, England..
    Ford, Ian
    Univ Glasgow, Glasgow G12 8QQ, Lanark, Scotland..
    Forouhi, Nita G.
    Univ Cambridge, Sch Clin Med, MRC, Epidemiol Unit,Inst Metab Sci, Cambridge Biomedical Campus, Cambridge CB2 0QQ, England..
    Gianfagna, Francesco
    Univ Insubria, Dept Clin & Expt Med, Res Ctr Epidemiol & Prevent Med, I-21100 Varese, Italy.;IRCCS, Dept Epidemiol & Prevent, Ist Neurol Mediterraneo Neuromed, I-86077 Pozzilli, Italy..
    Gonzalez, Carlos
    Catalan Inst Oncol ICO, Barcelona 08908, Spain..
    Grioni, Sara
    Epidemiol & Prevent Unit, I-20133 Milan, Italy..
    Hiller, Louise
    Univ Warwick, Warwick Clin Trials Unit, Gibbet Hill Rd, Coventry CV4 7AL, W Midlands, England..
    Jansson, Jan-Hakan
    Res Unit, S-93141 Skelleftea, Sweden.;Umea Univ, Dept Publ Hlth & Clin Med, S-90185 Umea, Sweden..
    Jorgensen, Marit E.
    Steno Diabet Ctr, DK-2820 Gentofte, Denmark.;Southern Denmark Univ, Natl Inst Publ Hlth, DK-1353 Odense, Denmark..
    Jukema, J. Wouter
    Umea Univ, Dept Publ Hlth & Clin Med, S-90185 Umea, Sweden..
    Kaaks, Rudolf
    German Canc Res Ctr, D-69120 Heidelberg, Germany..
    Kee, Frank
    Queens Univ Belfast, UK Clin Res Collaborat UKCRC, Ctr Excellence Publ Hlth, Belfast BT12 6BJ, Antrim, North Ireland..
    Kerrison, Nicola D.
    Univ Cambridge, Sch Clin Med, MRC, Epidemiol Unit,Inst Metab Sci, Cambridge Biomedical Campus, Cambridge CB2 0QQ, England..
    Key, Timothy J.
    Univ Oxford, S Parks Rd, Oxford OX1 2JD, England..
    Kontto, Jukka
    Natl Inst Hlth & Welfare, FI-00271 Helsinki, Finland..
    Kote-Jarai, Zsofia
    Inst Canc Res, Sutton SM2 5NG, Surrey, England..
    Kraja, Aldi T.
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63108 USA.;Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63108 USA..
    Kuulasmaa, Kari
    Natl Inst Hlth & Welfare, FI-00271 Helsinki, Finland..
    Kuusisto, Johanna
    Univ Eastern Finland, Inst Clin Med, Internal Med, FI-70211 Kuopio, Finland..
    Linneberg, Allan
    Res Ctr Prevent & Hlth, DK-2600 Copenhagen, Denmark.;Rigshosp, Dept Clin Expt, DK-2100 Copenhagen, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, DK-2200 Copenhagen, Denmark..
    Liu, Chunyu
    NHLBI, Framingham Heart Study, Populat Sci Branch, NIH, Bethesda, MD 20892 USA..
    Marenne, Galle
    Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England..
    Mohlke, Karen L.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA..
    Morris, Andrew P.
    Univ Liverpool, Dept Biostat, Liverpool L69 3GL, Merseyside, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England..
    Muir, Kenneth
    Univ Manchester, Inst Populat Hlth, Ctr Epidemiol, Oxford Rd, Manchester M13 9PT, Lancs, England.;Univ Warwick, Coventry CV4 7AL, W Midlands, England..
    Mueller-Nurasyid, Martina
    German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, D-85764 Neuherberg, Germany.;Univ Munich, Dept Med 1, D-80336 Munich, Germany.;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, D-80802 Munich, Germany..
    Munroe, Patricia B.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, Clin Pharmacol, London EC1M 6BQ, England..
    Navarro, Carmen
    CIBER Epidemiol & Salud Publ CIBERESP, Madrid 28029, Spain.;Murcia Reg Hlth Council, Dept Epidemiol, IMIB Arrixaca, Murcia 30008, Spain..
    Nielsen, Sune F.
    Univ Copenhagen, Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, DK-2730 Copenhagen, Denmark..
    Nilsson, Peter M.
    Lund Univ, S-20502 Malmo, Sweden..
    Nordestgaard, Borge G.
    Univ Copenhagen, Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, DK-2730 Copenhagen, Denmark..
    Packard, Chris J.
    Univ Glasgow, Glasgow G12 8QQ, Lanark, Scotland..
    Palli, Domenico
    Canc Res & Prevent Inst ISPO, I-50141 Florence, Italy..
    Panico, Salvatore
    Univ Naples Federico II, Dipartimento Med Clin & Chirurg, I-80131 Naples, Italy..
    Peloso, Gina M.
    Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    Perola, Markus
    Canc Res & Prevent Inst ISPO, I-50141 Florence, Italy.;Univ Helsinki, Inst Mol Med Finland FIMM, FI-00014 Helsinki, Finland..
    Peters, Annette
    DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, D-80802 Munich, Germany.;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, D-85764 Neuherberg, Germany..
    Poole, Christopher J.
    Univ Warwick, Coventry CV4 7AL, W Midlands, England.;Univ Hosp Coventry & Warwickshire, Arden Canc Ctr, Dept Med Oncol, Coventry CV2 2DX, W Midlands, England..
    Quiros, J. Ramn
    Publ Hlth Directorate, Oviedo 33006, Asturias, Spain..
    Rolandsson, Olov
    Umea Univ, S-90187 Umea, Sweden..
    Sacerdote, Carlotta
    Univ Turin, Citta Salute & Sci Hosp, Unit Canc Epidemiol, I-10126 Turin, Italy.;Ctr Canc Prevent CPO, I-10126 Turin, Italy.;Human Genet Fdn, I-10126 Turin, Italy..
    Salomaa, Veikko
    Natl Inst Hlth & Welfare, FI-00271 Helsinki, Finland..
    Sanchez, Mara-Jose
    CIBER Epidemiol & Salud Publ CIBERESP, Madrid 28029, Spain.;Univ Granada, Hosp Univ Granada, Inst Invest Biosanitaria Ibs GRANADA, Escuela Andaluza Salud Publ, Granada 18012, Spain..
    Sattar, Naveed
    Univ Glasgow, Glasgow G12 8QQ, Lanark, Scotland..
    Sharp, Stephen J.
    Univ Cambridge, Sch Clin Med, MRC, Epidemiol Unit,Inst Metab Sci, Cambridge Biomedical Campus, Cambridge CB2 0QQ, England..
    Sims, Rebecca
    Cardiff Univ, MRC Ctr, Inst Psychol Med & Clin Neurosci, Cardiff CF24 4HQ, S Glam, Wales..
    Slimani, Nadia
    Int Agcy Res Canc, F-69372 Lyon, France..
    Smith, Jennifer A.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Thompson, Deborah J.
    Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Strangeways Lab, Cambridge CB1 8RN, England..
    Trompet, Stella
    Leiden Univ, Med Ctr, NL-2333 AA Leiden, Netherlands..
    Tumino, Rosario
    ASP Ragusa, Civ MP Arezzo Hosp, Canc Registry & Histopathol Unit, I-97100 Ragusa, Italy..
    van der A, Daphne L.
    Natl Inst Publ Hlth & Environm RIVM, NL-3720 BA Bilthoven, Netherlands..
    van der Schouw, Yvonne T.
    Univ Med Ctr Utrecht, NL-3508 GA Utrecht, Netherlands..
    Virtamo, Jarmo
    Natl Inst Hlth & Welfare, FI-00271 Helsinki, Finland..
    Walker, Mark
    Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England..
    Walter, Klaudia
    Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England..
    Abraham, Jean E.
    Univ Cambridge, Dept Oncol, Strangeways Lab, Ctr Canc Genet Epidemiol, Worts Causeway, Cambridge CB1 8RN, England..
    Amundadottir, Laufey T.
    NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA..
    Aponte, Jennifer L.
    GlaxoSmithKline, PCPS, Genet, Res Triangle Pk, NC 27709 USA..
    Butterworth, Adams.
    Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England..
    Dupuis, Josee
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA..
    Easton, Douglas F.
    Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Strangeways Lab, Cambridge CB1 8RN, England.;Univ Cambridge, Dept Oncol, Strangeways Lab, Ctr Canc Genet Epidemiol, Worts Causeway, Cambridge CB1 8RN, England..
    Eeles, Rosalind A.
    Inst Canc Res, Sutton SM2 5NG, Surrey, England.;Royal Marsden NHS Fdn Trust, London SW3 6JJ, England.;Royal Marsden NHS Fdn Trust, Surrey SW3 6JJ, England..
    Erdmann, Jeanette
    Med Univ Lubeck, Inst Integrat & Expt Genom, D-23562 Lubeck, Germany..
    Franks, Paul W.
    Lund Univ, Genet & Mol Epidemiol Unit, Dept Clin Sci, SE-205 Malmo, Sweden.;Umea Univ, Dept Publ Hlth & Clin Med, S-90185 Umea, Sweden.;Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA..
    Frayling, Timothy M.
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter EX1 2LU, Devon, England..
    Hansen, Torben
    Univ Copenhagen, NovoNordisk Fdn, Fac Hlth & Med Sci, Ctr Basic Metab Res, DK-2200 Copenhagen, Denmark..
    Howson, Joanna M. M.
    Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England..
    Jorgensen, Torben
    Res Ctr Prevent & Hlth, DK-2600 Capital Region, Denmark.;Univ Copenhagen, Inst Hlth Sci, Dept Publ Hlth, DK-1014 Copenhagen, Denmark.;Aalborg Univ, Fac Med, DK-9220 Aalborg, Denmark..
    Kooner, Jaspal
    Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London SW3 6LY, England.;Imperial Coll Healthcare NHS Trust, London W2 1NY, England.;Ealing Hosp NHS Trust, Southall UB1 3HW, Middx, England..
    Laakso, Markku
    Univ Kuopio, Dept Med, FI-70211 Kuopio, Finland..
    Langenberg, Claudia
    Univ Cambridge, Sch Clin Med, MRC, Epidemiol Unit,Inst Metab Sci, Cambridge Biomedical Campus, Cambridge CB2 0QQ, England..
    McCarthy, Mark I.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab OCDEM, Oxford OX3 7LE, England..
    Pankow, James S.
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA..
    Pedersen, Oluf
    Univ Copenhagen, NovoNordisk Fdn, Fac Hlth & Med Sci, Ctr Basic Metab Res, DK-2200 Copenhagen, Denmark..
    Riboli, Elio
    Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London W2 1PG, England..
    Rotter, Jerome I.
    Harbor Univ Calif Los Angeles, Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA..
    Saleheen, Danish
    Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA..
    Samani, Nilesh J.
    Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England.;Glenfield Hosp, Natl Inst Hlth Res, Leicester Cardiovasc Biomed Res Unit, Leicester LE3 9QP, Leics, England..
    Schunkert, Heribert
    DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, D-80802 Munich, Germany.;Tech Univ Munich, Deutsch Herzzentrum Munchen, D-80636 Munich, Germany..
    Vollenweider, Peter
    Lausanne Univ Hosp CHUV, Dept Internal Med, Internal Med, BH10-462, CH-1011 Lausanne, Switzerland..
    O'Rahilly, Stephen
    Univ Cambridge, Wellcome Trust MRC Inst Metab Sci, Metab Res Labs, Cambridge CB2 0QQ, England.;MRC Metab Dis Unit, Cambridge CB2 0QQ, England.;Natl Inst Hlth Res, Cambridge Biomed Res Ctr, Cambridge CB2 0QQ, England..
    Deloukas, Panos
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England..
    Danesh, John
    Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England.;Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England..
    Goodarzi, Mark O.
    Cedars Sinai Med Ctr, Div Endocrinol Diabet & Metab, Los Angeles, CA 90048 USA..
    Kathiresan, Sekar
    Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Cardiol Div, Boston, MA 02114 USA.;Harvard Univ, Sch Med, Boston, MA 02114 USA..
    Meigs, James B.
    Massachusetts Gen Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02114 USA.;Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA..
    Ehm, Margaret G.
    GlaxoSmithKline, PCPS, Genet, Res Triangle Pk, NC 27709 USA..
    Wareham, Nicholas J.
    Univ Cambridge, Sch Clin Med, MRC, Epidemiol Unit,Inst Metab Sci, Cambridge Biomedical Campus, Cambridge CB2 0QQ, England..
    Waterworth, Dawn M.
    GlaxoSmithKline, PCPS, Genet, Philadelphia, PA 19104 USA..
    A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease2016Inngår i: Science Translational Medicine, ISSN 1946-6234, E-ISSN 1946-6242, Vol. 8, nr 341, artikkel-id 341ra76Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to guide development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in six genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow-up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association of those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low-frequency missense variant (Ala316Thr; rs10305492) in the gene encoding glucagon-like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomized controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process.

  • 266.
    Scott, Robert A.
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    Univ Cambridge, MRC Epidemiol Unit, Cambridge, England..
    Scott, Laura J.
    Univ Michigan, Dept Biostatist & Ctr Stat Genet, Ann Arbor, MI USA..
    Maegi, Reedik
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Marullo, Letizia
    Univ Ferrara, Dept Life Sci & Biotechnol, Ferrara, Italy..
    Gaulton, Kyle J.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Stanford Univ, Dept Genet, Stanford, CA USA..
    Kaakinen, Marika
    Imperial Coll London, Dept Genom Common Dis, London, England..
    Pervjakova, Natalia
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Pers, Tune H.
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Boston Childrens Hosp, Div Endocrinol, Ctr Basic & Translat Obes Res, Boston, MA USA.;Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark.;Statens Serum Inst, Dept Epidemiol Res, Copenhagen, Denmark..
    Johnson, Andrew D.
    Natl Heart Lung & Blood Inst, Div Intramural Res, Framingham Heart Study Populat Sci Branch, Framingham, MA USA..
    Eicher, John D.
    Natl Heart Lung & Blood Inst, Div Intramural Res, Framingham Heart Study Populat Sci Branch, Framingham, MA USA..
    Jackson, Anne U.
    Univ Michigan, Dept Biostatist & Ctr Stat Genet, Ann Arbor, MI USA..
    Ferreira, Teresa
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
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    Univ Michigan, Dept Biostatist & Ctr Stat Genet, Ann Arbor, MI USA..
    Ma, Clement
    Univ Michigan, Dept Biostatist & Ctr Stat Genet, Ann Arbor, MI USA..
    Steinthorsdottir, Valgerdur
    Amgen Inc, DECODE genet, Reykjavik, Iceland..
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    Amgen Inc, DECODE genet, Reykjavik, Iceland..
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    Harvard T H Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.;Harvard T H Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Brigham & Womens Hosp, Channing Div Network Med, Dept Med, Boston, MA USA.;Harvard Med Sch, Boston, MA USA..
    Van Zuydam, Natalie R.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
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    Univ Texas Hlth Sci Ctr, Sch Publ Hlth, Human Genet Ctr & Dept Epidemiol, Human Genet Environm Sci, Houston, TX USA.;Univ Texas Hlth Sci Ctr, Sch Biomed Informat, Sch Biomed Informat, Ctr Precis Hlth, Houston, TX USA..
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    Lund Univ, Univ Hosp Scania, Dept Clin Sci Malmo, Lund Univ Diabet Ctr, Lund, Sweden..
    Voight, Ben F.
    Univ Penn sylvania, Perelman Sch Med, Dept Pharm, Philadelphia, PA USA.;Univ Pennsylvania, Perelman Sch Med, Dept Genet, Philadelphia, PA USA.;Univ Pennsylvania, Perelman Sch Medi cine, Inst Translat Med & Therapeut, Philadelphia, PA USA..
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    Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Neuherberg, Germany.;German Ctr Diabet Res, Neuherberg, Germany..
    Mueller-Nurasyid, Martina
    German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Univ Hosp Grosshadern, Ludwig Maximilians Univ, Dep Med I, Munich, Germany.;Ludwig Maximilians Univ Munchen, Inst Med Informat, Genet Epidemiol, Biometry & Epidemiol, Munich, Germany.;Munich Heart Alliance, German Ctr Cardiovascular Dis, Munich, Germany..
    Ried, Janina S.
    German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany..
    Rayner, Nigel W.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Oxford Ctr Diabet, Endocrinol & Metab, Oxford, England.;Wellcome Trust Sanger Inst, Hinxton, England..
    Robertson, Neil
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Oxford Ctr Diabet, Endocrinol & Metab, Oxford, England..
    Karssen, Lennart C.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Polyomica S Hertogenbosch, Amsterdam, Netherlands..
    Van Leeuwen, Elisabeth M.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Willems, Sara M.
    Univ Cambridge, MRC Epidemiol Unit, Cambridge, England.;Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Fuchsberger, Christian
    Univ Michigan, Dept Biostatist & Ctr Stat Genet, Ann Arbor, MI USA..
    Kwan, Phoenix
    Univ Michigan, Dept Biostatist & Ctr Stat Genet, Ann Arbor, MI USA..
    Teslovich, Tanya M.
    Univ Michigan, Dept Biostatist & Ctr Stat Genet, Ann Arbor, MI USA..
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    Johns Hopkins Univ Sch Med, High Throughput Biol Ctr, Baltimore, MD USA..
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    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA..
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    Charles Bronfman Inst Personalized Med, Icahn Sch Med, Mt Sinai, New York, NY USA.;Icahn Sch Med, Genet Obes & Related Metab Traits Program, Mt Sinai, New York, NY USA..
    Dina, Christian
    Univ Nantes, CNRS, Inst Thorax, Ctr Hosp Univ Nantes, Nantes, France..
    Thuillier, Dorothee
    Lille Inst Biol, European Genom Inst Diabet, Lille, France.;Univ Lille, CNRS UMR 8199, European Genom Inst Diabet EGID, Inst Pasteur Lille, Lille, France..
    Yengo, Loic
    Lille Inst Biol, European Genom Inst Diabet, Lille, France.;Univ Lille, CNRS UMR 8199, European Genom Inst Diabet EGID, Inst Pasteur Lille, Lille, France..
    Jiang, Longda
    Imperial Coll London, Dept Genom Common Dis, London, England..
    Sparso, Thomas
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Kestler, Hans A.
    Fritz Lipmann Inst, Leibniz Inst Aging, Jena, Germany.;Univ Ulm, Inst Med Syst Biol, Ulm, Germany..
    Chheda, Himanshu
    Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland..
    Eisele, Lewin
    Univ Hosp Essen, Inst Med Informat, Biometry & Epidemiol, Essen, Germany..
    Gustafsson, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
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    Karolinska Inst, Dept Med Solna, Cardiovascular Med Unit, Stockholm, Sweden.;Sci Life Lab, Stockholm, Sweden.;Stockholm Univ, Dept Numer Anal & Comp Sci, Stockholm, Sweden..
    Strawbridge, Rona J.
    Karolinska Inst, Dept Med Solna, Cardiovascular Med Unit, Stockholm, Sweden..
    Benediktsson, Rafn
    Univ Iceland, Fac Med, Reykjavik, Iceland.;Landspitali Univ Hosp, Reykjavik, Iceland..
    Hreidarsson, Astradur B.
    Landspitali Univ Hosp, Reykjavik, Iceland..
    Kong, Augustine
    Amgen Inc, DECODE genet, Reykjavik, Iceland..
    Sigurdsson, Gunnar
    Landspitali Univ Hosp, Reykjavik, Iceland.;Iceland Heart Assoc, Kopavogur, Iceland..
    Kerrison, Nicola D.
    Univ Cambridge, MRC Epidemiol Unit, Cambridge, England..
    Luan, Jian'an
    Univ Cambridge, MRC Epidemiol Unit, Cambridge, England..
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    Harvard T H Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.;Harvard T H Chan Sch Publ Hlth, Dept Biostatist, Boston, MA USA..
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    Munich Heart Alliance, German Ctr Cardiovascular Dis, Munich, Germany.;Fritz Lipmann Inst, Leibniz Inst Aging, Jena, Germany.;Inst Human Genet, Helmholtz Zentrum Munchen, Neuherberg, Germany. Tech Univ Munich, Inst Human Genet, Munich, Germany..
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    German Ctr Diabet Res, Neuherberg, Germany.;Heinrich Heine Univ, Fac Med, Dept Endocrinol & Diabet, Dusseldorf, Germany.;Heinrich Heine Univ Dusseldorf, Leibniz Inst Diabet Res, German Diabet Ctr, Inst Clin Diabetol, Dusseldorf, Germany..
    Thorand, Barbara
    German Ctr Diabet Res, Neuherberg, Germany..
    Esko, Tonu
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Boston Childrens Hosp, Divis Genet & Endocrinol, Boston, MA USA.;Natl Heart Lung & Blood Inst, Framingham Heart Study, Framingham, MA USA..
    Mihailov, Evelin
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Fox, Caroline
    Harvard Med Sch, Divis Endocrinol, Diabet & Hypertens, Brigham & Womens Hosp, Boston, MA USA..
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    Boston Univ Sch Publ Hlth, Dept Biostat, Boston, MA USA..
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    Boston Univ Sch Publ Hlth, Data Coordinating Ctr, Boston, MA USA..
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    Folkhalsan Res Ctr, Helsinki, Finland.;Dept Social Serv & Hlth Care, Pietarsaari, Finland..
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    Lund Univ, Univ Hosp Scania, Dept Clin Sci Malmo, Lund Univ Diabet Ctr, Lund, Sweden..
    Tuomi, Tiinamaija
    Folkhalsan Res Ctr, Helsinki, Finland.;Univ Helsinki, Helsinki Univ Hosp, Dept Med, Helsinki, Finland..
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    Univ N Carolina, Dept Biostatist, Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA..
    Pankow, James S.
    Univ Minnesota, Divis Epidemiol Community Hlth, Minneapolis, MN USA..
    Grarup, Niels
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Have, Christian T.
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Jorgensen, Marit E.
    Steno Diabet Ctr, Gentofte, Denmark..
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    Capital Region Denmark, Res Ctr Prevent & Hlth, Copenhagen, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.;Aalborg Univ, Fac Med, Aalborg, Denmark..
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    Capital Region Denmark, Res Ctr Prevent & Hlth, Copenhagen, Denmark.;Copenhagen Univ Hosp, Rigshospitalet, Copenhagen, Denmark. Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, DK-1168 Copenhagen, Denmark..
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    NW Univ Feinberg Sch Med, Dept Prevent Med, Chicago, IL USA..
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    Harvard T H Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
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    Harvard T H Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.;Harvard T H Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Brigham & Womens Hosp, Channing Div Network Med, Dept Med, Boston, MA USA.;Harvard Med Sch, Boston, MA USA.;Harvard T H Chan Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Boston, MA USA..
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    Harvard T H Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.;Harvard T H Chan Sch Publ Hlth, Dept Biostatist, Boston, MA USA.;Harvard T H Chan Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Boston, MA USA..
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    Harvard T H Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Brigham & Womens Hosp, Channing Div Network Med, Dept Med, Boston, MA USA.;Harvard Med Sch, Boston, MA USA..
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    Wellcome Trust Sanger Inst, Hinxton, England..
    Owen, Katharine R.
    Univ Oxford, Oxford Ctr Diabet, Endocrinol & Metab, Oxford, England.;Natl Inst Hlth Res Oxford Biomed Res Ctr, Churchill Hosp, Oxford, England..
    Perry, John R. B.
    Univ Cambridge, MRC Epidemiol Unit, Cambridge, England..
    Wood, Andrew R.
    Univ Exeter Med Sch, Univ Exeter, Genet Complex Traits, Exeter, Devon, England..
    Zeggini, Eleftheria
    Wellcome Trust Sanger Inst, Hinxton, England..
    Tajes-Fernandes, Juan
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Abecasis, Goncalo R.
    Univ Michigan, Dept Biostatist & Ctr Stat Genet, Ann Arbor, MI USA..
    Bonnycastle, Lori L.
    Natl Human Genome Res Inst, Natl Inst Hlth, Bethesda, MD USA..
    Chines, Peter S.
    Natl Human Genome Res Inst, Natl Inst Hlth, Bethesda, MD USA..
    Stringham, Heather M.
    Univ Michigan, Dept Biostatist & Ctr Stat Genet, Ann Arbor, MI USA..
    Koistinen, Heikki A.
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.;Univ Helsinki, Helsinki Univ Cent Hosp, Dept Med & Abdominal Ctr, Endocrinol, Helsinki, Finland.;Biomedicum Helsinki 2U, Minerva Fdn Inst Med Res, Helsinki, Finland..
    Kinnunen, Leena
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.;Univ Helsinki, Helsinki Univ Cent Hosp, Dept Med & Abdominal Ctr, Endocrinol, Helsinki, Finland.;Biomedicum Helsinki 2U, Minerva Fdn Inst Med Res, Helsinki, Finland..
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    Karolinska Inst, Dept Med Solna, Cardiovascular Med Unit, Stockholm, Sweden.;Sci Life Lab, Stockholm, Sweden..
    Muehleisen, Thomas W.
    Univ Bonn, Inst Human Genet, Bonn, Germany.;Univ Bonn, Dept Genom, Life Brain Ctr, Bonn, Germany..
    Noethen, Markus M.
    Univ Bonn, Inst Human Genet, Bonn, Germany.;Univ Bonn, Dept Genom, Life Brain Ctr, Bonn, Germany..
    Pechlivanis, Sonali
    Univ Hosp Essen, Inst Med Informat, Biometry & Epidemiol, Essen, Germany..
    Baldassarre, Damiano
    Ist Ricovero Cura Carattere Sci, Ctr Cardiologico Monzino, Milan, Italy.;Univ Milan, Dipartimento Sci Farmacol Biomol, Milan, Italy..
    Gertow, Karl
    Karolinska Inst, Dept Med Solna, Cardiovascular Med Unit, Stockholm, Sweden..
    Humphries, Steve E.
    UCL, Inst Cardiovascular Sci, BHF Labs, Cardiovascular Genet, London, England..
    Tremoli, Elena
    Ist Ricovero Cura Carattere Sci, Ctr Cardiologico Monzino, Milan, Italy.;Univ Milan, Dipartimento Sci Farmacol Biomol, Milan, Italy..
    Klopp, Norman
    Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Hannover Med Sch, Hannover Unified Biobank, Hannover, Germany..
    Meyer, Julia
    German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany..
    Steinbach, Gerald
    Univ Ulm, Dept Clin Chem & Cent Lab, Ulm, Germany..
    Wennauer, Roman
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Eriksson, Johan G.
    Folkhalsan Res Ctr, Helsinki, Finland.;Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.;Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland.;Helsinki Univ Cent Hosp, Unit Gen Practice, Helsinki, Finland..
    Mannisto, Satu
    Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland..
    Peltonen, Leena
    Wellcome Trust Sanger Inst, Hinxton, England.;Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland.;Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.;Broad Inst & Harvard, Cambridge, MA USA..
    Tikkanen, Emmi
    Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland.;Univ Helsinki, Hjelt Inst, Dept Publ Hlth, Helsinki, Finland..
    Charpentier, Guillaume
    Corbeil Essonnes Hosp, Endocrinol Diabetol Unit, Corbeil Essonnes, France..
    Eury, Elodie
    Univ Lille, CNRS UMR 8199, European Genom Inst Diabet EGID, Inst Pasteur Lille, Lille, France..
    Lobbens, Stephane
    Univ Lille, CNRS UMR 8199, European Genom Inst Diabet EGID, Inst Pasteur Lille, Lille, France..
    Gigante, Bruna
    Inst Environm Medi cine, Karolinska Inst, Divis Cardiovascular Epidemiol, Stockholm, Sweden..
    Leander, Karin
    Inst Environm Medi cine, Karolinska Inst, Divis Cardiovascular Epidemiol, Stockholm, Sweden..
    McLeod, Olga
    Karolinska Inst, Dept Med Solna, Cardiovascular Med Unit, Stockholm, Sweden..
    Bottinger, Erwin P.
    Charles Bronfman Inst Personalized Med, Icahn Sch Med, Mt Sinai, New York, NY USA..
    Gottesman, Omri
    Charles Bronfman Inst Personalized Med, Icahn Sch Med, Mt Sinai, New York, NY USA..
    Ruderfer, Douglas
    Icahn Sch Med, Dept Psychiat, Divis Psychiat Genom, Mt Sinai, New York, NY USA..
    Blueher, Matthias
    Univ Leipzig, IFB Adiposity Dis, Leipzig, Germany.;Univ Leipzig, Dept Med, Leipzig, Germany..
    Kovacs, Peter
    Univ Leipzig, IFB Adiposity Dis, Leipzig, Germany.;Univ Leipzig, Dept Med, Leipzig, Germany..
    Tonjes, Anke
    Univ Leipzig, IFB Adiposity Dis, Leipzig, Germany.;Univ Leipzig, Dept Med, Leipzig, Germany..
    Maruthur, Nisa M.
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.;Johns Hopkins Bloomberg Sch Med, Dept Med, Divis Gen Internal Med, Baltimore, MD USA.;Johns Hopkins Univ, Welch Ctr Prevent, Epidemiol & Clin Res, Baltimore, MD USA..
    Scapoli, Chiara
    Univ Ferrara, Dept Life Sci & Biotechnol, Ferrara, Italy..
    Erbel, Raimund
    Univ Hosp Essen, Inst Med Informat, Biometry & Epidemiol, Essen, Germany..
    Joeckel, Karl-Heinz
    Univ Hosp Essen, Inst Med Informat, Biometry & Epidemiol, Essen, Germany..
    Moebus, Susanne
    Univ Hosp Essen, Inst Med Informat, Biometry & Epidemiol, Essen, Germany..
    De Faire, Ulf
    Inst Environm Medi cine, Karolinska Inst, Divis Cardiovascular Epidemiol, Stockholm, Sweden..
    Hamsten, Anders
    Karolinska Inst, Dept Med Solna, Cardiovascular Med Unit, Stockholm, Sweden..
    Stumvoll, Michael
    Univ Leipzig, IFB Adiposity Dis, Leipzig, Germany.;Univ Leipzig, Dept Med, Leipzig, Germany..
    Deloukas, Panagiotis
    Wellcome Trust Sanger Inst, Hinxton, England.;Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England..
    Donnelly, Peter J.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Dept Stat, Oxford, England..
    Frayling, Timothy M.
    Univ Exeter Med Sch, Univ Exeter, Genet Complex Traits, Exeter, Devon, England..
    Hattersley, Andrew T.
    Univ Exeter Med Sch, Inst Biomed & Clin Sci, Exeter, Devon, England..
    Ripatti, Samuli
    Wellcome Trust Sanger Inst, Hinxton, England.;Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland.;Univ Helsinki, Hjelt Inst, Dept Publ Hlth, Helsinki, Finland.;Natl Inst Hlth & Welf, Publ Hlth Genom Unit, Helsinki, Finland..
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland..
    Pedersen, Nancy L.
    Karolinska Inst tutet, Dept Med Epidemiol & Biostatist, Stockholm, Sweden..
    Boehm, Bernhard O.
    Univ Med Ctr Ulm, Dept Internal Med, Divis Endocrinol & Diabet, Ulm, Germany.;Nanyang Technol Univ, Imperial Coll London, Lee Kong Chian Sch Med, Singapore, Singapore..
    Bergman, Richard N.
    Cedars Sinai Med Ctr, Diabetes & Obes Res Inst, Los Angeles, CA USA..
    Collins, Francis S.
    Natl Human Genome Res Inst, Natl Inst Hlth, Bethesda, MD USA..
    Mohlke, Karen L.
    Univ N Carolina, Dept Genet, Chapel Hill, NC USA..
    Tuomilehto, Jaakko
    Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.;Dasman Diabet Inst, Dasman, Kuwait.;Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria.;King Abdulaziz Univ, Diabetes Res Grp, Jeddah, Saudi Arabia..
    Hansen, Torben
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark.;Univ So Denmark, Fac Hlth Sci, Odense, Denmark..
    Pedersen, Oluf
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Barroso, Ines
    Wellcome Trust Sanger Inst, Hinxton, England.;Addenbrookes Hosp Cambridge, Wellcome Trust MRC Inst Metab Sci, Hlth Res Cambridge Biomed Res Ctr, Cambridge, England.;Univ Cambridge Metab Res Labs, Wellcome Trust MRC Inst Metab Sci, Hlth Res Cambridge Biomed Res Ctr, Cambridge, England..
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Lindgren, Cecilia M.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Broad Inst & Harvard, Cambridge, MA USA..
    Cauchi, Stephane
    Lille Inst Biol, European Genom Inst Diabet, Lille, France..
    Froguel, Philippe
    Imperial Coll London, Dept Genom Common Dis, London, England.;Lille Inst Biol, European Genom Inst Diabet, Lille, France.;Univ Lille, CNRS UMR 8199, European Genom Inst Diabet EGID, Inst Pasteur Lille, Lille, France..
    Loos, Ruth J. F.
    Charles Bronfman Inst Personalized Med, Icahn Sch Med, Mt Sinai, New York, NY USA.;Icahn Sch Med, Genet Obes & Related Metab Traits Program, Mt Sinai, New York, NY USA.;Mindich Child Hlth & Dev Inst, Icahn Sch Med, Mt Sinai, New York, NY USA..
    Balkau, Beverley
    INSERM, CESP, UMR 1018, Villejuif, France.;Univ Paris Sud, UMR 1018, Villejuif, France..
    Boeing, Heiner
    German Inst Human Nutr Potsdam Rehbrucke, Nuthetal, Germany..
    Franks, Paul W.
    Lund Univ, Malmo, Sweden.;Umea Univ, Umea, Sweden..
    Gurrea, Aurelio Barricarte
    Navarra Publ Hlth Inst, Pamplona, Spain.;Navarra Inst Hlth Res, Pamplona, Spain.;CIBER Epidemiol & Publ Hlth, Madrid, Spain..
    Palli, Domenico
    Canc Res & Prevent Inst, Florence, Italy..
    Van der Schouw, Yvonne T.
    Univ Med Ctr Utrecht, Utrecht, Netherlands..
    Altshuler, David
    Broad Inst & Harvard, Cambridge, MA USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA USA.;Harvard Med Sch, Dept Med, Boston, MA USA.;Harvard Med Sch, Dept Genet, Boston, MA USA.;Harvard Med Sch, Dept Mol Biol, Boston, MA USA.;Massachusetts Gen Hosp, Diabet Unit, Boston, MA USA..
    Groop, Leif C.
    Lund Univ, Univ Hosp Scania, Dept Clin Sci Malmo, Lund Univ Diabet Ctr, Lund, Sweden.;Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland..
    Langenberg, Claudia
    Univ Cambridge, MRC Epidemiol Unit, Cambridge, England..
    Wareham, Nicholas J.
    Univ Cambridge, MRC Epidemiol Unit, Cambridge, England..
    Sijbrands, Eric
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Van Duijn, Cornelia M.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Healthy Ageing & Ctr Med Syst Biol, Netherlands Consortium, Netherlands Genom Initiat, Rotterdam, Netherlands..
    Florez, Jose C.
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Harvard Med Sch, Dept Med, Boston, MA USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Diabet Unit, Boston, MA USA..
    Meigs, James B.
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Amgen Inc, DECODE genet, Reykjavik, Iceland.;Harvard Med Sch, Dept Med, Boston, MA USA.;Massachusetts Gen Hosp, Gen Med Divis, Boston, MA USA..
    Boerwinkle, Eric
    Univ Texas Hlth Sci Ctr, Human Genet Ctr, Houston, TX USA.;Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX USA..
    Gieger, Christian
    Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Neuherberg, Germany.;German Res Ctr Environm Hlth, Inst Epidemiol II, Helmholtz Zentrum Munchen, Neuherberg, Germany..
    Strauch, Konstantin
    German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Ludwig Maximilians Univ Munchen, Inst Med Informat, Genet Epidemiol, Biometry & Epidemiol, Munich, Germany..
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Univ Tartu, Inst Mol & Cell Biol, Tartu, Estonia..
    Morris, Andrew D.
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland..
    Palmer, Colin N. A.
    Univ Dundee, Biomed Res Inst, Ninewells Hosp, Cardiovascular & Diabet Med, Dundee, Scotland..
    Hu, Frank B.
    Harvard T H Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.;Harvard T H Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Brigham & Womens Hosp, Channing Div Network Med, Dept Med, Boston, MA USA.;Harvard Med Sch, Boston, MA USA..
    Thorsteinsdottir, Unnur
    Amgen Inc, DECODE genet, Reykjavik, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Stefansson, Kari
    Amgen Inc, DECODE genet, Reykjavik, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Dupuis, Josee
    Boston Univ Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Morris, Andrew P.
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.;Univ Liverpool, Dept Mol & Clin Pharmacol, Liverpool, Merseyside, England..
    Boehnke, Michael
    Univ Michigan, Dept Biostatist & Ctr Stat Genet, Ann Arbor, MI USA..
    McCarthy, Mark I.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Oxford Ctr Diabet, Endocrinol & Metab, Oxford, England.;Natl Inst Hlth Res Oxford Biomed Res Ctr, Churchill Hosp, Oxford, England..
    Prokopenko, Inga
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Imperial Coll London, Dept Genom Common Dis, London, England.;Univ Oxford, Oxford Ctr Diabet, Endocrinol & Metab, Oxford, England..
    An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans2017Inngår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 66, nr 11, s. 2888-2902Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    To characterize type 2 diabetes (T2D)-associated variation across the allele frequency spectrum, we conducted a meta-analysis of genome-wide association data from 26,676 T2D case and 132,532 control subjects of European ancestry after imputation using the 1000 Genomes multiethnic reference panel. Promising association signals were followed up in additional data sets (of 14,545 or 7,397 T2D case and 38,994 or 71,604 control subjects). We identified 13 novel T2D-associated loci (P < 5 x 10(-8)), including variants near the GLP2R, GIP, and HLA-DQA1 genes. Our analysis brought the total number of independent T2D associations to 128 distinct signals at 113 loci. Despite substantially increased sample size and more complete coverage of low-frequency variation, all novel associations were driven by common single nucleotide variants. Credible sets of potentially causal variants were generally larger than those based on imputation with earlier reference panels, consistent with resolution of causal signals to common risk haplotypes. Stratification of T2D-associated loci based on T2D-related quantitative trait associations revealed tissue-specific enrichment of regulatory annotations in pancreatic islet enhancers for loci influencing insulin secretion and in adipocytes, monocytes, and hepatocytes for insulin action-associated loci. These findings highlight the predominant role played by common variants of modest effect and the diversity of biological mechanisms influencing T2D pathophysiology.

  • 267.
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    Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia;UCL, Inst Cardiovasc Sci, London, England;UCL, British Heart Fdn Res Accelerator, London, England.
    Henry, Albert
    UCL, Inst Cardiovasc Sci, London, England;UCL, British Heart Fdn Res Accelerator, London, England;UCL, Inst Hlth Informat, London, England.
    Roselli, Carolina
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA;Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
    Lin, Honghuang
    Boston Univ, Sch Med, Dept Med, Sect Computat Biomed, Boston, MA 02118 USA;NHLBI, Framingham, MA USA;Boston Univ Framingham Heart Study, Framingham, MA USA.
    Sveinbjornsson, Gardar
    Amgen Inc, deCODE Genet, Sturlugata 8, IS-101 Reykjavik, Iceland.
    Fatemifar, Ghazaleh
    UCL, British Heart Fdn Res Accelerator, London, England;UCL, Inst Hlth Informat, London, England;UCL, Hlth Data Res UK London, London, England.
    Hedman, Asa K.
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden.
    Wilk, Jemma B.
    Pfizer Worldwide Res & Dev, 1 Portland St, Cambridge, MA USA.
    Morley, Michael P.
    Univ Penn, Perelman Sch Med, Penn Cardiovasc Inst, Philadelphia, PA 19104 USA.
    Chaffin, Mark D.
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA.
    Helgadottir, Anna
    Amgen Inc, deCODE Genet, Sturlugata 8, IS-101 Reykjavik, Iceland.
    Verweij, Niek
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA;Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
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    Imperial Coll London, Dept Epidemiol & Biostat, St Marys Campus, London W2 1PG, England;Imperial Coll London, Dept Epidemiol & Biostat, MRC PHE Ctr Environm & Hlth, St Marys Campus, London W2 1PG, England.
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    Lund Univ, Dept Clin Sci, Malmo, Sweden.
    Andersson, Charlotte
    NHLBI, Framingham, MA USA;Boston Univ Framingham Heart Study, Framingham, MA USA;Herlev Gentofte Hosp, Dept Cardiol, Herlev Ringvej 57, DK-2650 Herlev, Denmark.
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    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA;Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
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    Karolinska Inst, Sect Family Med & Primary Care, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden;Dalarna Univ, Sch Hlth & Social Sci, Falun, Sweden.
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    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Biggs, Mary L.
    Univ Washington, Dept Biostat, Seattle, WA 98195 USA;Univ Washington, Dept Med, Seattle, WA USA.
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    Emory Univ, Dept Med, Med Ctr, Div Cardiol, Atlanta, GA 30322 USA.
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    Univ Penn, Perelman Sch Med, Penn Cardiovasc Inst, Philadelphia, PA 19104 USA.
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    Univ Texas Sch Publ Hlth, Dept Epidemiol Human Genet & Environm Sci, Houston, TX USA.
    Buckbinder, Leonard
    Pfizer Worldwide Res & Dev, 1 Portland St, Cambridge, MA USA.
    Carey, David J.
    Geisinger, Dept Mol & Funct Genom, Danville, PA USA.
    Chasman, Daniel I.
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA 02115 USA.
    Chen, Xing
    Pfizer Worldwide Res & Dev, 1 Portland St, Cambridge, MA USA.
    Chen, Xu
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Chung, Jonathan
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Chutkow, William
    Novartis Inst Biomed Res, Cambridge, MA USA.
    Cook, James P.
    Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.
    Delgado, Graciela E.
    Heidelberg Univ, Med Fac Mannheim, Dept Med Nephrol Hypertensiol Endocrinol Diabetol, Heidelberg, Germany.
    Denaxas, Spiros
    UCL, British Heart Fdn Res Accelerator, London, England;UCL, Inst Hlth Informat, London, England;UCL, Hlth Data Res UK London, London, England;UCL, Natl Inst Hlth Res, Hosp Biomed Res Ctr, London, England;Alan Turing Inst, London, England.
    Doney, Alexander S.
    Univ Dundee, Ninewells Hosp & Med Sch, Div Mol & Clin Med, Dundee DD1 9SY, Scotland.
    Doerr, Marcus
    Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany.
    Dudley, Samuel C.
    Univ Minnesota, Dept Med, Cardiovasc Div, Minneapolis, MN USA.
    Dunn, Michael E.
    Regeneron Pharmaceut, Cardiovasc Res, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Engstrom, Gunnar
    Lund Univ, Dept Clin Sci, Malmo, Sweden.
    Esko, Tonu
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA;Univ Tartu, Inst Genom, Estonian Genome Ctr, EE-51010 Tartu, Estonia.
    Felix, Stephan B.
    Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany.
    Finan, Chris
    UCL, Inst Cardiovasc Sci, London, England;UCL, British Heart Fdn Res Accelerator, London, England.
    Ford, Ian
    Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.
    Ghanbari, Mohsen
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
    Ghasemi, Sahar
    DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany;Univ Med Greifswald, Inst Community Med, Greifswald, Germany.
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Giulianini, Franco
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.
    Gottdiener, John S.
    Univ Maryland, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21201 USA.
    Gross, Stefan
    Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany.
    Gudbjartsson, Daniel F.
    Amgen Inc, deCODE Genet, Sturlugata 8, IS-101 Reykjavik, Iceland;Univ Iceland, Sch Engn & Nat Sci, IS-101 Reykjavik, Iceland.
    Gutmann, Rebecca
    Univ Iowa, Carver Coll Med, Div Cardiovasc Med, Iowa City, IA USA.
    Haggerty, Christopher M.
    Geisinger, Dept Mol & Funct Genom, Danville, PA USA.
    van der Harst, Pim
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands;Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands;ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands.
    Hyde, Craig L.
    Pfizer Worldwide Res & Dev, 1 Portland St, Cambridge, MA USA.
    Ingelsson, Erik
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA;Stanford Univ, Stanford Diabet Res Ctr, Stanford, CA 94305 USA.
    Jukema, J. Wouter
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands;LUMC, Einthoven Lab Expt Vasc Med, Leiden, Netherlands.
    Kavousi, Maryam
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
    Khaw, Kay-Tee
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB2 0QQ, England.
    Kleber, Marcus E.
    Heidelberg Univ, Med Fac Mannheim, Dept Med Nephrol Hypertensiol Endocrinol Diabetol, Heidelberg, Germany.
    Kober, Lars
    Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, Copenhagen, Denmark.
    Koekemoer, Andrea
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England;Glenfield Hosp, NIHR Leicester Biomed Res Ctr, Leicester, Leics, England.
    Langenberg, Claudia
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Lindgren, Cecilia M.
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA;Univ Oxford, Li Ka Shing Ctr Hlth Informat & Discovery, Big Data Inst, Oxford, England;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
    London, Barry
    Univ Iowa, Div Cardiovasc Med, Iowa City, IA USA;Univ Iowa, Abboud Cardiovasc Res Ctr, Iowa City, IA USA.
    Lotta, Luca A.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England.
    Lovering, Ruth C.
    UCL, Inst Cardiovasc Sci, London, England;UCL, British Heart Fdn Res Accelerator, London, England.
    Luan, Jian'an
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England.
    Magnusson, Patrik
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
    Margulies, Kenneth B.
    Univ Penn, Perelman Sch Med, Penn Cardiovasc Inst, Philadelphia, PA 19104 USA.
    Maerz, Winfried
    Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England;Synlab Holding Deutschland GmbH, Synlab Acad, Mannheim, Germany;Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria.
    Melander, Olle
    Lund Univ, Dept Internal Med, Clin Sci, Malmo, Sweden;Skane Univ Hosp, Malmo, Sweden.
    Mordi, Ify R.
    Univ Dundee, Ninewells Hosp & Med Sch, Div Mol & Clin Med, Dundee DD1 9SY, Scotland.
    Morgan, Thomas
    Novartis Inst Biomed Res, Cambridge, MA USA;Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA.
    Morris, Andrew D.
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
    Morris, Andrew P.
    Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
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    Univ Texas Sch Publ Hlth, Dept Epidemiol Human Genet & Environm Sci, Houston, TX USA.
    Nagle, Michael W.
    Pfizer Worldwide Res & Dev, 1 Portland St, Cambridge, MA USA.
    Nelson, Christopher P.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England;Glenfield Hosp, NIHR Leicester Biomed Res Ctr, Leicester, Leics, England.
    Niessner, Alexander
    Med Univ Vienna, Div Cardiol, Dept Internal Med 2, Vienna, Austria.
    Niiranen, Teemu
    Natl Inst Hlth & Welf, Helsinki, Finland;Turku Univ Hosp, Dept Med, Turku, Finland;Univ Turku, Turku, Finland.
    O'Donoghue, Michelle L.
    Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA.
    Owens, Anjali T.
    Univ Penn, Perelman Sch Med, Penn Cardiovasc Inst, Philadelphia, PA 19104 USA.
    Palmer, Colin N. A.
    Univ Dundee, Ninewells Hosp & Med Sch, Div Mol & Clin Med, Dundee DD1 9SY, Scotland.
    Parry, Helen M.
    Univ Dundee, Ninewells Hosp & Med Sch, Div Mol & Clin Med, Dundee DD1 9SY, Scotland.
    Perola, Markus
    Natl Inst Hlth & Welf, Helsinki, Finland.
    Portilla-Fernandez, Eliana
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands;Erasmus MC, Dept Internal Med, Div Vasc Med & Pharmacol, Rotterdam, Netherlands.
    Psaty, Bruce M.
    Univ Washington, Dept Med Epidemiol & Hlth Serv, Seattle, WA 98195 USA;Kaiser Permanente Washington, Kaiser Permanente Washington Hlth Res Inst, Seattle, WA USA.
    Rice, Kenneth M.
    Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
    Ridker, Paul M.
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA 02115 USA.
    Romaine, Simon P. R.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England;Glenfield Hosp, NIHR Leicester Biomed Res Ctr, Leicester, Leics, England.
    Rotter, Jerome I.
    Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Dept Pediat, Torrance, CA 90509 USA;Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Dept Med, Torrance, CA 90509 USA.
    Salo, Perttu
    Natl Inst Hlth & Welf, Helsinki, Finland.
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Helsinki, Finland.
    van Setten, Jessica
    Univ Utrecht, Univ Med Ctr Utrecht, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands.
    Shalaby, Alaa A.
    Univ Pittsburgh, Med Ctr, Dept Med, Div Cardiol, Pittsburgh, PA USA;VA Pittsburgh HCS, Pittsburgh, VA USA.
    Smelser, Diane T.
    Geisinger, Dept Mol & Funct Genom, Danville, PA USA.
    Smith, Nicholas L.
    Kaiser Permanente Washington, Kaiser Permanente Washington Hlth Res Inst, Seattle, WA USA;Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA;Dept Vet Affairs Off Res & Dev, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA.
    Stender, Steen
    Copenhagen Univ Hosp, Dept Clin Biochem, Copenhagen, Denmark.
    Stott, David J.
    Univ Glasgow, Coll Med Vet & Life Sci, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
    Svensson, Per
    Karolinska Inst, Dept Clin Sci & Educ, Sodersjukhuset, Stockholm, Sweden;Soder Sjukhuset, Dept Cardiol, Stockholm, Sweden.
    Tammesoo, Mari-Liis
    Univ Tartu, Inst Genom, Estonian Genome Ctr, EE-51010 Tartu, Estonia.
    Taylor, Kent D.
    Harbor UCLA Med Ctr, LABiomed, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA;Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90502 USA.
    Teder-Laving, Maris
    Univ Tartu, Inst Genom, Estonian Genome Ctr, EE-51010 Tartu, Estonia.
    Teumer, Alexander
    DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany;Univ Med Greifswald, Inst Community Med, Greifswald, Germany.
    Thorgeirsson, Gudmundur
    Amgen Inc, deCODE Genet, Sturlugata 8, IS-101 Reykjavik, Iceland;Natl Univ Hosp Iceland, Landspitali, Dept Internal Med, Div Cardiol, IS-101 Reykjavik, Iceland.
    Thorsteinsdottir, Unnur
    Amgen Inc, deCODE Genet, Sturlugata 8, IS-101 Reykjavik, Iceland;Univ Iceland, Dept Med, Fac Med, Saemundargata 2, IS-101 Reykjavik, Iceland.
    Torp-Pedersen, Christian
    Aalborg Univ Hosp, Dept Epidemiol & Biostat, Aalborg, Denmark;Aalborg Univ Hosp, Dept Hlth Sci & Technol, Aalborg, Denmark;Aalborg Univ Hosp, Dept Cardiol, Aalborg, Denmark.
    Trompet, Stella
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands;Leiden Univ, Med Ctr, Dept Internal Med, Sect Gerontol & Geriatr, Leiden, Netherlands.
    Tyl, Benoit
    Servier Cardiovasc Ctr Therapeut Innovat, Translat & Clin Res, 50 Rue Carnot, F-92284 Suresnes, France.
    Uitterlinden, Andre G.
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands;Erasmus MC, Univ Med Ctr Rotterdam, Dept Internal Med, Rotterdam, Netherlands.
    Veluchamy, Abirami
    Univ Dundee, Ninewells Hosp & Med Sch, Div Mol & Clin Med, Dundee DD1 9SY, Scotland.
    Voelker, Uwe
    DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany;Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany.
    Voors, Adriaan A.
    Boston Univ, Sch Med, Dept Med, Sect Computat Biomed, Boston, MA 02118 USA.
    Wang, Xiaosong
    Novartis Inst Biomed Res, Cambridge, MA USA.
    Wareham, Nicholas J.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England.
    Waterworth, Dawn
    GlaxoSmithKline, Human Genet, Collegeville, PA USA.
    Weeke, Peter E.
    Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, Copenhagen, Denmark.
    Weiss, Raul
    Ohio State Univ, Med Ctr, Dept Internal Med, Div Cardiovasc Med, Columbus, OH 43210 USA.
    Wiggins, Kerri L.
    Univ Washington, Dept Med, Seattle, WA USA.
    Xing, Heming
    Novartis Inst Biomed Res, Cambridge, MA USA.
    Yerges-Armstrong, Laura M.
    GlaxoSmithKline, Human Genet, Collegeville, PA USA.
    Yu, Bing
    Univ Texas Sch Publ Hlth, Dept Epidemiol Human Genet & Environm Sci, Houston, TX USA.
    Zannad, Faiez
    Univ Lorraine, CHU Nancy, INSERM, F-54500 Nancy, France;Inst Lorrain Coeur & Vaisseaux, INI CRCT F CRIN, F-54500 Nancy, France.
    Zhao, Jing Hua
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England.
    Hemingway, Harry
    UCL, British Heart Fdn Res Accelerator, London, England;UCL, Inst Hlth Informat, London, England;UCL, Hlth Data Res UK London, London, England;Univ Glasgow, BHF Cardiovasc Res Ctr, Glasgow, Lanark, Scotland.
    Samani, Nilesh J.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England;Glenfield Hosp, NIHR Leicester Biomed Res Ctr, Leicester, Leics, England.
    McMurray, John J. V.
    Univ Glasgow, BHF Cardiovasc Res Ctr, Glasgow, Lanark, Scotland.
    Yang, Jian
    Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia;Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia.
    Visscher, Peter M.
    Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia;Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia.
    Newton-Cheh, Christopher
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
    Malarstig, Anders
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden;Pfizer Worldwide Res & Dev, 1 Portland St, Cambridge, MA USA.
    Holm, Hilma
    Amgen Inc, deCODE Genet, Sturlugata 8, IS-101 Reykjavik, Iceland.
    Lubitz, Steven A.
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA;Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
    Sattar, Naveed
    Univ Glasgow, BHF Cardiovasc Res Ctr, Glasgow, Lanark, Scotland.
    Holmes, Michael V.
    Univ Oxford, Med Res Council, Populat Hlth Res Unit, Oxford, England;Univ Oxford, Big Data Inst, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England;Univ Oxford, Big Data Inst, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Oxford, England;Oxford Univ Hosp, Oxford Biomed Res Ctr, Natl Inst Hlth Res, Oxford, England.
    Cappola, Thomas P.
    Univ Penn, Perelman Sch Med, Penn Cardiovasc Inst, Philadelphia, PA 19104 USA.
    Asselbergs, Folkert W.
    UCL, Inst Cardiovasc Sci, London, England;UCL, British Heart Fdn Res Accelerator, London, England;Univ Utrecht, Univ Med Ctr Utrecht, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands.
    Hingorani, Aroon D.
    UCL, Inst Cardiovasc Sci, London, England;UCL, British Heart Fdn Res Accelerator, London, England.
    Kuchenbaecker, Karoline
    UCL, Div Psychiat, London W1T 7NF, England;UCL, Genet Inst, London WC1E 6BT, England.
    Ellinor, Patrick T.
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA;Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
    Lang, Chim C.
    Univ Dundee, Ninewells Hosp & Med Sch, Div Mol & Clin Med, Dundee DD1 9SY, Scotland.
    Stefansson, Kari
    Amgen Inc, deCODE Genet, Sturlugata 8, IS-101 Reykjavik, Iceland;Univ Iceland, Dept Med, Fac Med, Saemundargata 2, IS-101 Reykjavik, Iceland.
    Smith, J. Gustav
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA;Lund Univ, Dept Cardiol, Clin Sci, Lund, Sweden;Skane Univ Hosp, Lund, Sweden;Lund Univ, Wallenberg Ctr Mol Med, Lund, Sweden;Lund Univ, Ctr Diabet, Lund, Sweden.
    Vasan, Ramachandran S.
    NHLBI, Framingham, MA USA;Boston Univ Framingham Heart Study, Framingham, MA USA;Boston Univ, Sch Med, Dept Med, Sect Cardiol, Boston, MA 02118 USA;Boston Univ, Sch Med, Dept Med, Sect Prevent Med, Boston, MA 02118 USA;Boston Univ, Sch Med, Dept Med, Sect Epidemiol, Boston, MA 02118 USA;Boston Univ, Sch Publ Hlth, Dept Med, Sect Cardiol, Boston, MA USA;Boston Univ, Sch Publ Hlth, Dept Med, Sect Prevent Med, Boston, MA USA;Boston Univ, Sch Publ Hlth, Dept Med, Sect Epidemiol, Boston, MA USA.
    Swerdlow, Daniel I.
    UCL, Inst Cardiovasc Sci, London, England.
    Lumbers, R. Thomas
    UCL, British Heart Fdn Res Accelerator, London, England;UCL, Inst Hlth Informat, London, England;UCL, Hlth Data Res UK London, London, England;St Bartholomews Hosp, Barts Heart Ctr, London, England.
    Abecasis, Goncalo
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Backman, Joshua
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Bai, Xiaodong
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Balasubramanian, Suganthi
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Banerjee, Nilanjana
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Baras, Aris
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Barnard, Leland
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Beechert, Christina
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Blumenfeld, Andrew
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Cantor, Michael
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Chai, Yating
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Coppola, Giovanni
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Damask, Amy
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Dewey, Frederick
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Economides, Aris
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Eom, Gisu
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Forsythe, Caitlin
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Fuller, Erin D.
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Gu, Zhenhua
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Gurski, Lauren
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Guzzardo, Paloma M.
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Habegger, Lukas
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Hahn, Young
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Hawes, Alicia
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    van Hout, Cristopher
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Jones, Marcus B.
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Khalid, Shareef
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Lattari, Michael
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Li, Alexander
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Lin, Nan
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Liu, Daren
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Lopez, Alexander
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Manoochehri, Kia
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Marchini, Jonathan
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Marcketta, Anthony
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Maxwell, Evan K.
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    McCarthy, Shane
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Mitnaul, Lyndon J.
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    O'Dushlaine, Colm
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Overton, John D.
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Padilla, Maria Sotiropoulos
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Paulding, Charles
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Penn, John
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Pradhan, Manasi
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Reid, Jeffrey G.
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Schleicher, Thomas D.
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Schurmann, Claudia
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Shuldiner, Alan
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Staples, Jeffrey C.
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Sun, Dylan
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Toledo, Karina
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Ulloa, Ricardo H.
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Widom, Louis
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Wolf, Sarah E.
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Yadav, Ashish
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Ye, Bin
    Regeneron Genet Ctr, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
    Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure2020Inngår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 11, nr 1, artikkel-id 163Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.

  • 268.
    Shungin, Dmitry
    et al.
    Lund Univ, Diabet Ctr, Skane Univ Hosp, Dept Clin Sci,Genet & Mol Epidemiol Unit, Malmo, Sweden.;Umea Univ, Dept Odontol, Umea, Sweden.;Umea Univ, Dept Publ Hlth & Clin Med, Unit Med, Umea, Sweden.;MIT, Broad Inst, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;Harvard Univ, Cambridge, MA 02138 USA..
    Deng, Wei Q.
    Univ Toronto, Dept Stat Sci, Toronto, ON, Canada..
    Varga, Tibor V.
    Lund Univ, Diabet Ctr, Skane Univ Hosp, Dept Clin Sci,Genet & Mol Epidemiol Unit, Malmo, Sweden.;Univ Copenhagen, Fac Hlth & Med Sci, Translat Dis Syst Biol Grp, Novo Nordisk Fdn Ctr Prot Res, Copenhagen, Denmark.;Lund Univ, Exercise Physiol Grp, Dept Hlth Sci, Lund, Sweden..
    Luan, Jian'an
    Univ Cambridge, Inst Metab Sci, Addenbrookes Hosp, MRC Epidemiol Unit, Cambridge, England..
    Mihailov, Evelin
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Univ Tartu, Inst Mol & Cell Biol, Tartu, Estonia..
    Morris, Andrew P.
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England..
    Forouhi, Nita G.
    Univ Cambridge, Inst Metab Sci, Addenbrookes Hosp, MRC Epidemiol Unit, Cambridge, England..
    Lindgren, Cecilia
    MIT, Broad Inst, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;Harvard Univ, Cambridge, MA 02138 USA.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Magnusson, Patrik K. E.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Hallmans, Göran
    Umea Univ, Dept Biobank Res, Umea, Sweden..
    Chu, Audrey Y.
    Harvard Med Sch, Boston, MA USA..
    Justice, Anne E.
    Univ North Carolina Chapel Hill, Dept Epidemiol, Chapel Hill, NC USA..
    Graff, Mariaelisa
    Univ North Carolina Chapel Hill, Dept Epidemiol, Chapel Hill, NC USA..
    Winkler, Thomas W.
    Univ Regensburg, Dept Genet Epidemiol, Regensburg, DE, Germany..
    Rose, Lynda M.
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA..
    Langenberg, Claudia
    Univ Cambridge, Inst Metab Sci, Addenbrookes Hosp, MRC Epidemiol Unit, Cambridge, England.;UCL, Dept Epidemiol & Publ Hlth, London, England..
    Cupples, L. Adrienne
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.;NHLBI Framingham Heart Study, Framingham, MA USA..
    Ridker, Paul M.
    Harvard Med Sch, Boston, MA USA.;Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA..
    Wareham, Nicholas J.
    Univ Cambridge, Inst Metab Sci, Addenbrookes Hosp, MRC Epidemiol Unit, Cambridge, England..
    Ong, Ken K.
    Univ Cambridge, Inst Metab Sci, Addenbrookes Hosp, MRC Epidemiol Unit, Cambridge, England..
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY USA.;Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY USA.;Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY USA..
    Chasman, Daniel I.
    Harvard Med Sch, Boston, MA USA.;Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA..
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA..
    Kilpeläinen, Tuomas O.
    Univ Copenhagen, Fac Hlth & Med Sci, Sect Metab Genet, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Scott, Robert A.
    Univ Cambridge, Inst Metab Sci, Addenbrookes Hosp, MRC Epidemiol Unit, Cambridge, England..
    Magi, Reedik
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Pare, Guillaume
    McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada..
    Franks, Paul W.
    Lund Univ, Diabet Ctr, Skane Univ Hosp, Dept Clin Sci,Genet & Mol Epidemiol Unit, Malmo, Sweden.;Umea Univ, Dept Publ Hlth & Clin Med, Unit Med, Umea, Sweden.;Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Univ Oxford, Radcliff Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions2017Inngår i: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 13, nr 6, artikkel-id e1006812Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Phenotypic variance heterogeneity across genotypes at a single nucleotide polymorphism (SNP) may reflect underlying gene-environment (GxE) or gene-gene interactions. We modeled variance heterogeneity for blood lipids and BMI in up to 44,211 participants and investigated relationships between variance effects (P-v), GxE interaction effects (with smoking and physical activity), and marginal genetic effects (P-m). Correlations between P-v and P-m were stronger for SNPs with established marginal effects (Spearman's rho = 0.401 for triglycerides, and rho = 0.236 for BMI) compared to all SNPs. When P-v and P-m were compared for all pruned SNPs, only BMI was statistically significant (Spearman's rho = 0.010). Overall, SNPs with established marginal effects were overrepresented in the nominally significant part of the P-v distribution (P-binomial < 0.05). SNPs from the top 1% of the P-m distribution for BMI had more significant P-v values (Pmann-Whitney = 1.46x10(-5)), and the odds ratio of SNPs with nominally significant (< 0.05) P-m and P-v was 1.33 (95% CI: 1.12, 1.57) for BMI. Moreover, BMI SNPs with nominally significant GxE interaction P-values (Pint < 0.05) were enriched with nominally significant P-v values (P-binomial = 8.63x10(-9) and 8.52x10(-7) for SNP x smoking and SNP x physical activity, respectively). We conclude that some loci with strong marginal effects may be good candidates for GxE, and variance-based prioritization can be used to identify them.

  • 269. Shungin, Dmitry
    et al.
    Winkler, Thomas W
    Croteau-Chonka, Damien C
    Ferreira, Teresa
    Locke, Adam E
    Mägi, Reedik
    Strawbridge, Rona J
    Pers, Tune H
    Fischer, Krista
    Justice, Anne E
    Workalemahu, Tsegaselassie
    Wu, Joseph M W
    Buchkovich, Martin L
    Heard-Costa, Nancy L
    Roman, Tamara S
    Drong, Alexander W
    Song, Ci
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Gustafsson, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Day, Felix R
    Esko, Tonu
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Kutalik, Zoltán
    Luan, Jian'an
    Randall, Joshua C
    Scherag, André
    Vedantam, Sailaja
    Wood, Andrew R
    Chen, Jin
    Fehrmann, Rudolf
    Karjalainen, Juha
    Kahali, Bratati
    Liu, Ching-Ti
    Schmidt, Ellen M
    Absher, Devin
    Amin, Najaf
    Anderson, Denise
    Beekman, Marian
    Bragg-Gresham, Jennifer L
    Buyske, Steven
    Demirkan, Ayse
    Ehret, Georg B
    Feitosa, Mary F
    Goel, Anuj
    Jackson, Anne U
    Johnson, Toby
    Kleber, Marcus E
    Kristiansson, Kati
    Mangino, Massimo
    Mateo Leach, Irene
    Medina-Gomez, Carolina
    Palmer, Cameron D
    Pasko, Dorota
    Pechlivanis, Sonali
    Peters, Marjolein J
    Prokopenko, Inga
    Stančáková, Alena
    Ju Sung, Yun
    Tanaka, Toshiko
    Teumer, Alexander
    Van Vliet-Ostaptchouk, Jana V
    Yengo, Loïc
    Zhang, Weihua
    Albrecht, Eva
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Arscott, Gillian M
    Bandinelli, Stefania
    Barrett, Amy
    Bellis, Claire
    Bennett, Amanda J
    Berne, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Blüher, Matthias
    Böhringer, Stefan
    Bonnet, Fabrice
    Böttcher, Yvonne
    Bruinenberg, Marcel
    Carba, Delia B
    Caspersen, Ida H
    Clarke, Robert
    Daw, E Warwick
    Deelen, Joris
    Deelman, Ewa
    Delgado, Graciela
    Doney, Alex S F
    Eklund, Niina
    Erdos, Michael R
    Estrada, Karol
    Eury, Elodie
    Friedrich, Nele
    Garcia, Melissa E
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Gigante, Bruna
    Go, Alan S
    Golay, Alain
    Grallert, Harald
    Grammer, Tanja B
    Gräßler, Jürgen
    Grewal, Jagvir
    Groves, Christopher J
    Haller, Toomas
    Hallmans, Goran
    Hartman, Catharina A
    Hassinen, Maija
    Hayward, Caroline
    Heikkilä, Kauko
    Herzig, Karl-Heinz
    Helmer, Quinta
    Hillege, Hans L
    Holmen, Oddgeir
    Hunt, Steven C
    Isaacs, Aaron
    Ittermann, Till
    James, Alan L
    Johansson, Ingegerd
    Juliusdottir, Thorhildur
    Kalafati, Ioanna-Panagiota
    Kinnunen, Leena
    Koenig, Wolfgang
    Kooner, Ishminder K
    Kratzer, Wolfgang
    Lamina, Claudia
    Leander, Karin
    Lee, Nanette R
    Lichtner, Peter
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Lindström, Jaana
    Lobbens, Stéphane
    Lorentzon, Mattias
    Mach, François
    Magnusson, Patrik K E
    Mahajan, Anubha
    McArdle, Wendy L
    Menni, Cristina
    Merger, Sigrun
    Mihailov, Evelin
    Milani, Lili
    Mills, Rebecca
    Moayyeri, Alireza
    Monda, Keri L
    Mooijaart, Simon P
    Mühleisen, Thomas W
    Mulas, Antonella
    Müller, Gabriele
    Müller-Nurasyid, Martina
    Nagaraja, Ramaiah
    Nalls, Michael A
    Narisu, Narisu
    Glorioso, Nicola
    Nolte, Ilja M
    Olden, Matthias
    Rayner, Nigel W
    Renstrom, Frida
    Ried, Janina S
    Robertson, Neil R
    Rose, Lynda M
    Sanna, Serena
    Scharnagl, Hubert
    Scholtens, Salome
    Sennblad, Bengt
    Seufferlein, Thomas
    Sitlani, Colleen M
    Vernon Smith, Albert
    Stirrups, Kathleen
    Stringham, Heather M
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Swertz, Morris A
    Swift, Amy J
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Tayo, Bamidele O
    Thorand, Barbara
    Thorleifsson, Gudmar
    Tomaschitz, Andreas
    Troffa, Chiara
    van Oort, Floor V A
    Verweij, Niek
    Vonk, Judith M
    Waite, Lindsay L
    Wennauer, Roman
    Wilsgaard, Tom
    Wojczynski, Mary K
    Wong, Andrew
    Zhang, Qunyuan
    Hua Zhao, Jing
    Brennan, Eoin P
    Choi, Murim
    Eriksson, Per
    Folkersen, Lasse
    Franco-Cereceda, Anders
    Gharavi, Ali G
    Hedman, Åsa K
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Hivert, Marie-France
    Huang, Jinyan
    Kanoni, Stavroula
    Karpe, Fredrik
    Keildson, Sarah
    Kiryluk, Krzysztof
    Liang, Liming
    Lifton, Richard P
    Ma, Baoshan
    McKnight, Amy J
    McPherson, Ruth
    Metspalu, Andres
    Min, Josine L
    Moffatt, Miriam F
    Montgomery, Grant W
    Murabito, Joanne M
    Nicholson, George
    Nyholt, Dale R
    Olsson, Christian
    Perry, John R B
    Reinmaa, Eva
    Salem, Rany M
    Sandholm, Niina
    Schadt, Eric E
    Scott, Robert A
    Stolk, Lisette
    Vallejo, Edgar E
    Westra, Harm-Jan
    Zondervan, Krina T
    Amouyel, Philippe
    Arveiler, Dominique
    Bakker, Stephan J L
    Beilby, John
    Bergman, Richard N
    Blangero, John
    Brown, Morris J
    Burnier, Michel
    Campbell, Harry
    Chakravarti, Aravinda
    Chines, Peter S
    Claudi-Boehm, Simone
    Collins, Francis S
    Crawford, Dana C
    Danesh, John
    de Faire, Ulf
    de Geus, Eco J C
    Dörr, Marcus
    Erbel, Raimund
    Eriksson, Johan G
    Farrall, Martin
    Ferrannini, Ele
    Ferrières, Jean
    Forouhi, Nita G
    Forrester, Terrence
    Franco, Oscar H
    Gansevoort, Ron T
    Gieger, Christian
    Gudnason, Vilmundur
    Haiman, Christopher A
    Harris, Tamara B
    Hattersley, Andrew T
    Heliövaara, Markku
    Hicks, Andrew A
    Hingorani, Aroon D
    Hoffmann, Wolfgang
    Hofman, Albert
    Homuth, Georg
    Humphries, Steve E
    Hyppönen, Elina
    Illig, Thomas
    Jarvelin, Marjo-Riitta
    Johansen, Berit
    Jousilahti, Pekka
    Jula, Antti M
    Kaprio, Jaakko
    Kee, Frank
    Keinanen-Kiukaanniemi, Sirkka M
    Kooner, Jaspal S
    Kooperberg, Charles
    Kovacs, Peter
    Kraja, Aldi T
    Kumari, Meena
    Kuulasmaa, Kari
    Kuusisto, Johanna
    Lakka, Timo A
    Langenberg, Claudia
    Le Marchand, Loic
    Lehtimäki, Terho
    Lyssenko, Valeriya
    Männistö, Satu
    Marette, André
    Matise, Tara C
    McKenzie, Colin A
    McKnight, Barbara
    Musk, Arthur W
    Möhlenkamp, Stefan
    Morris, Andrew D
    Nelis, Mari
    Ohlsson, Claes
    Oldehinkel, Albertine J
    Ong, Ken K
    Palmer, Lyle J
    Penninx, Brenda W
    Peters, Annette
    Pramstaller, Peter P
    Raitakari, Olli T
    Rankinen, Tuomo
    Rao, D C
    Rice, Treva K
    Ridker, Paul M
    Ritchie, Marylyn D
    Rudan, Igor
    Salomaa, Veikko
    Samani, Nilesh J
    Saramies, Jouko
    Sarzynski, Mark A
    Schwarz, Peter E H
    Shuldiner, Alan R
    Staessen, Jan A
    Steinthorsdottir, Valgerdur
    Stolk, Ronald P
    Strauch, Konstantin
    Tönjes, Anke
    Tremblay, Angelo
    Tremoli, Elena
    Vohl, Marie-Claude
    Völker, Uwe
    Vollenweider, Peter
    Wilson, James F
    Witteman, Jacqueline C
    Adair, Linda S
    Bochud, Murielle
    Boehm, Bernhard O
    Bornstein, Stefan R
    Bouchard, Claude
    Cauchi, Stéphane
    Caulfield, Mark J
    Chambers, John C
    Chasman, Daniel I
    Cooper, Richard S
    Dedoussis, George
    Ferrucci, Luigi
    Froguel, Philippe
    Grabe, Hans-Jörgen
    Hamsten, Anders
    Hui, Jennie
    Hveem, Kristian
    Jöckel, Karl-Heinz
    Kivimaki, Mika
    Kuh, Diana
    Laakso, Markku
    Liu, Yongmei
    März, Winfried
    Munroe, Patricia B
    Njølstad, Inger
    Oostra, Ben A
    Palmer, Colin N A
    Pedersen, Nancy L
    Perola, Markus
    Pérusse, Louis
    Peters, Ulrike
    Power, Chris
    Quertermous, Thomas
    Rauramaa, Rainer
    Rivadeneira, Fernando
    Saaristo, Timo E
    Saleheen, Danish
    Sinisalo, Juha
    Slagboom, P Eline
    Snieder, Harold
    Spector, Tim D
    Thorsteinsdottir, Unnur
    Stumvoll, Michael
    Tuomilehto, Jaakko
    Uitterlinden, André G
    Uusitupa, Matti
    van der Harst, Pim
    Veronesi, Giovanni
    Walker, Mark
    Wareham, Nicholas J
    Watkins, Hugh
    Wichmann, H-Erich
    Abecasis, Goncalo R
    Assimes, Themistocles L
    Berndt, Sonja I
    Boehnke, Michael
    Borecki, Ingrid B
    Deloukas, Panos
    Franke, Lude
    Frayling, Timothy M
    Groop, Leif C
    Hunter, David J
    Kaplan, Robert C
    O'Connell, Jeffrey R
    Qi, Lu
    Schlessinger, David
    Strachan, David P
    Stefansson, Kari
    van Duijn, Cornelia M
    Willer, Cristen J
    Visscher, Peter M
    Yang, Jian
    Hirschhorn, Joel N
    Zillikens, M Carola
    McCarthy, Mark I
    Speliotes, Elizabeth K
    North, Kari E
    Fox, Caroline S
    Barroso, Inês
    Franks, Paul W
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Heid, Iris M
    Loos, Ruth J F
    Cupples, L Adrienne
    Morris, Andrew P
    Lindgren, Cecilia M
    Mohlke, Karen L
    New genetic loci link adipose and insulin biology to body fat distribution2015Inngår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 518, nr 7538, s. 187-196Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

  • 270. Sjöberg, B
    et al.
    Qureshi, A R
    Heimbürger, O
    Stenvinkel, P
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Bárány, P
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Association between levels of pentraxin 3 and incidence of chronic kidney disease in the elderly2016Inngår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 279, nr 2, s. 173-179Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: Higher levels of the novel inflammatory marker pentraxin 3 (PTX3) predict cardiovascular mortality in patients with chronic kidney disease (CKD). Yet, whether PTX3 predicts worsening of kidney function has been less well studied. We therefore investigated the associations between PTX3 levels, kidney disease measures and CKD incidence.

    METHODS: Cross-sectional associations between serum PTX3 levels, urinary albumin/creatinine ratio (ACR) and cystatin C-estimated glomerular filtration rate (GFR) were assessed in two independent community-based cohorts of elderly subjects: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS, n = 768, 51% women, mean age 75 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 651, mean age 77 years). The longitudinal association between PTX3 level at baseline and incident CKD (GFR <60 mL( ) min(-1)  1.73 m(-) ²) was also analysed (number of events/number at risk: PIVUS 229/746, ULSAM 206/315).

    RESULTS: PTX3 levels were inversely associated with GFR [PIVUS: B-coefficient per 1 SD increase -0.16, 95% confidence interval (CI) -0.23 to -0.10, P < 0.001; ULSAM: B-coefficient per 1 SD increase -0.09, 95% CI -0.16 to -0.01, P < 0.05], but not ACR, after adjusting for age, gender, C-reactive protein and prevalent cardiovascular disease in cross-sectional analyses. In longitudinal analyses, PTX3 levels predicted incident CKD after 5 years in both cohorts [PIVUS: multivariable odds ratio (OR) 1.21, 95% CI 1.01-1.45, P < 0.05; ULSAM: multivariable OR 1.37, 95% CI 1.07-1.77, P < 0.05].

    CONCLUSIONS: Higher PTX3 levels are associated with lower GFR and independently predict incident CKD in elderly men and women. Our data confirm and extend previous evidence suggesting that inflammatory processes are activated in the early stages of CKD and drive impairment of kidney function. Circulating PTX3 appears to be a promising biomarker of kidney disease.

  • 271.
    Sjögren, Per
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Montse, Rachel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Lampa, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Salihovic, Samira
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    van Bavel, Bert
    MTM Research Centre, Örebro University, Örebro, Sweden.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Lind, P. Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Circulating levels of perfluoroalkyl substances are associated with dietary patterns: A cross sectional study in elderly Swedish men and women2016Inngår i: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 150, s. 59-65Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: In our daily life, we are exposed to perfluoroalkyl substances (PFAS) with possible health implications. The main exposure route for these substances is diet but comparative studies on how dietary habits influence exposure are lacking. Objectives: To examine the relations between blood levels of PFAS and adherence to three predefined dietary patterns (a WHO recommended diet, a Mediterranean-like diet, and a Low-Carbohydrate High Protein (LCHP) diet) in an elderly Swedish population. Methods: Dietary data from 7-day food records and serum concentrations of PFAS were obtained from a 70-year-old Swedish population (n=844), the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. The Healthy Diet Indicator score (based on WHO recommendations), the Mediterranean Diet Score and LCHP score were used to assess adherence. Multivariate linear regression was used to assess the associations between eight major PFAS and adherence to each dietary pattern. Results: The WHO recommended diet was positively associated with perfluorohexane sulfonic acid (PFHxS). The LCHP diet was positively related to four out of eight PFAS; namely, perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA) and perfluoroundecanoic acid (PFUnDA). The Mediterranean-like diet was positively associated with most PFAS; namely perfluorooctanoic acid (PFOA), perfluorooctane sulfonamide (PFOSA), PFHxS, PFNA, PFDA, and PFUnDA. Conclusions: All dietary patterns were positively associated with blood levels of PFAS. The highest body burden of PFAS was found in individuals with high adherence to a Mediterranean-like diet, whilst individuals who more closely followed the officially recommended diet displayed a lower body burden of these compounds.

  • 272. Soler Artigas, María
    et al.
    Wain, Louise V
    Miller, Suzanne
    Kheirallah, Abdul Kader
    Huffman, Jennifer E
    Ntalla, Ioanna
    Shrine, Nick
    Obeidat, Ma'en
    Trochet, Holly
    McArdle, Wendy L
    Alves, Alexessander Couto
    Hui, Jennie
    Zhao, Jing Hua
    Joshi, Peter K
    Teumer, Alexander
    Albrecht, Eva
    Imboden, Medea
    Rawal, Rajesh
    Lopez, Lorna M
    Marten, Jonathan
    Enroth, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Surakka, Ida
    Polasek, Ozren
    Lyytikäinen, Leo-Pekka
    Granell, Raquel
    Hysi, Pirro G
    Flexeder, Claudia
    Mahajan, Anubha
    Beilby, John
    Bossé, Yohan
    Brandsma, Corry-Anke
    Campbell, Harry
    Gieger, Christian
    Gläser, Sven
    González, Juan R
    Grallert, Harald
    Hammond, Chris J
    Harris, Sarah E
    Hartikainen, Anna-Liisa
    Heliövaara, Markku
    Henderson, John
    Hocking, Lynne
    Horikoshi, Momoko
    Hutri-Kähönen, Nina
    Ingelsson, Erik
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Johansson, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Kemp, John P
    Kolcic, Ivana
    Kumar, Ashish
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Melén, Erik
    Musk, Arthur W
    Navarro, Pau
    Nickle, David C
    Padmanabhan, Sandosh
    Raitakari, Olli T
    Ried, Janina S
    Ripatti, Samuli
    Schulz, Holger
    Scott, Robert A
    Sin, Don D
    Starr, John M
    Viñuela, Ana
    Völzke, Henry
    Wild, Sarah H
    Wright, Alan F
    Zemunik, Tatijana
    Jarvis, Deborah L
    Spector, Tim D
    Evans, David M
    Lehtimäki, Terho
    Vitart, Veronique
    Kähönen, Mika
    Gyllensten, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Rudan, Igor
    Deary, Ian J
    Karrasch, Stefan
    Probst-Hensch, Nicole M
    Heinrich, Joachim
    Stubbe, Beate
    Wilson, James F
    Wareham, Nicholas J
    James, Alan L
    Morris, Andrew P
    Jarvelin, Marjo-Riitta
    Hayward, Caroline
    Sayers, Ian
    Strachan, David P
    Hall, Ian P
    Tobin, Martin D
    Sixteen new lung function signals identified through 1000 Genomes Project reference panel imputation2015Inngår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 6, artikkel-id 8658Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Lung function measures are used in the diagnosis of chronic obstructive pulmonary disease. In 38,199 European ancestry individuals, we studied genome-wide association of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC with 1000 Genomes Project (phase 1)-imputed genotypes and followed up top associations in 54,550 Europeans. We identify 14 novel loci (P<5 × 10(-8)) in or near ENSA, RNU5F-1, KCNS3, AK097794, ASTN2, LHX3, CCDC91, TBX3, TRIP11, RIN3, TEKT5, LTBP4, MN1 and AP1S2, and two novel signals at known loci NPNT and GPR126, providing a basis for new understanding of the genetic determinants of these traits and pulmonary diseases in which they are altered.

  • 273.
    Song, Ci
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
    Chang, Z
    Magnusson, P K E
    Ingelsson, Erik
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
    Pedersen, N L
    Genetic factors may play a prominent role in the development of coronary heart disease dependent on important environmental factors2014Inngår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 275, nr 6, s. 631-639Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: The aim of the study was to examine whether various lifestyle factors modify genetic influences on coronary heart disease (CHD).

    DESIGN: The effect of lifestyle factors [including smoking, sedentary lifestyle, alcohol intake and body mass index (BMI)] on risk of CHD was evaluated via Cox regression models in a twin study of gene-environment interaction. Using structure equation modelling, we estimated genetic variance of CHD dependent on lifestyle factors.

    SUBJECTS: In total, 51 065 same-sex twins from 25 715 twin pairs born before 1958 and registered in the Swedish Twin Registry were eligible for this study. During the 40-year follow-up, 7264 incident CHD events were recorded.

    RESULTS: Smoking, sedentary lifestyle and above average BMI were significantly associated with increased CHD incidence. The heritability of CHD decreased with increasing age, as well as with increasing levels of BMI, in both men and women.

    CONCLUSIONS: The difference in the genetic component of CHD as a function of BMI suggests that genetic factors may play a more prominent role for disease development in the absence of important environmental factors. Increased knowledge of gene-environment interactions will be important for a full understanding of the aetiology of CHD.

  • 274.
    Spracklen, Cassandra N.
    et al.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
    Karaderi, Tugce
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7FZ, England;Eastern Mediterranean Univ, Fac Arts & Sci, Dept Biol Sci, Gazimagusa, Cyprus;Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Prot Res, DK-2200 Copenhagen, Denmark;Tech Univ Denmark, DTU Hlth Technol, DK-2800 Lyngby, Denmark.
    Yaghootkar, Hanieh
    Univ Exeter, Sch Med, Royal Devon & Exeter Hosp, Genet Complex Traits, Exeter EX2 5DW, Devon, England;Univ Westminster, Sch Life Sci, Res Ctr Optimal Hlth, London, England.
    Schurmann, Claudia
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
    Fine, Rebecca S.
    Harvard Med Sch, Dept Genet, Boston, MA 02115 USA;Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA;Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
    Kutalik, Zoltan
    Univ Exeter, Sch Med, Royal Devon & Exeter Hosp, Genet Complex Traits, Exeter EX2 5DW, Devon, England;Univ Lausanne, Univ Ctr Primary Care & Publ Hlth, CH-1010 Lausanne, Switzerland;Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.
    Preuss, Michael H.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
    Lu, Yingchang
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA;Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Vanderbilt Epidemiol Ctr, Div Epidemiol,Dept Med,Sch Med, Nashville, TN 37203 USA;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA.
    Wittemans, Laura B. L.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7FZ, England;Univ Cambridge, MRC Epidemiol Unit, Cambridge CB2 0QQ, England.
    Adair, Linda S.
    Univ North Carolina Chapel Hill, Carolina Populat Ctr, Chapel Hill, NC 27516 USA.
    Allison, Matthew
    Univ Calif San Diego, Dept Family Med & Publ Hlth, San Diego, CA 92093 USA.
    Amin, Najaf
    Erasmus MC, Dept Epidemiol, NL-3015 CN Rotterdam, Netherlands.
    Auer, Paul L.
    Univ Wisconsin, Joseph J Zilber Sch Publ Hlth, Milwaukee, WI 53201 USA.
    Bartz, Traci M.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA;Univ Washington, Dept Biostat, Seattle, WA 98101 USA.
    Blueher, Matthias
    Univ Leipzig, Med Dept Endocrinol Nephrol Rheumatol 3, Leipzig, Germany.
    Boehnke, Michael
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
    Borja, Judith B.
    Off Populat Studies Fdn Inc, Cebu, Philippines;Univ San Carlos, Dept Nutr & Dietet, Cebu, Philippines.
    Bork-Jensen, Jette
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2200 Copenhagen, Denmark.
    Broer, Linda
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands.
    Chasman, Daniel I.
    Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA;Harvard Med Sch, Boston, MA 02115 USA.
    Chen, Yii-Der Ida
    Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.
    Chirstofidou, Paraskevi
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England.
    Demirkan, Ayse
    Erasmus MC, Dept Epidemiol, NL-3015 CN Rotterdam, Netherlands.
    van Duijn, Cornelia M.
    Erasmus MC, Dept Epidemiol, NL-3015 CN Rotterdam, Netherlands.
    Feitosa, Mary F.
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.
    Garcia, Melissa E.
    NHLBI, Bldg 10, Bethesda, MD 20892 USA.
    Graff, Mariaelisa
    Univ North Carolina Chapel Hill, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA;Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA.
    Grallert, Harald
    Helmholtz Zentrum Munchen, Res Ctr Environm Hlth, Inst Epidemiol, Res Unit Mol Epidemiol, D-85764 Munich, Germany;German Ctr Diabet Res, D-85765 Munich, Germany.
    Grarup, Niels
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2200 Copenhagen, Denmark.
    Guo, Xiuqing
    Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.
    Haesser, Jeffrey
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
    Hansen, Torben
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2200 Copenhagen, Denmark.
    Harris, Tamara B.
    NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA.
    Highland, Heather M.
    Univ North Carolina Chapel Hill, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA.
    Hong, Jaeyoung
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
    Ikram, M. Arfan
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands.
    Ingelsson, Erik
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Stanford Univ, Dept Med, Div Cardiovasc Med, Palo Alto, CA 94304 USA;Stanford Univ, Stanford Cardiovasc Inst, Palo Alto, CA 94304 USA;Stanford Univ, Stanford Diabet Res Ctr, Stanford, CA 94305 USA.
    Jackson, Rebecca
    Ohio State Univ, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA.
    Jousilahti, Pekka
    Natl Inst Hlth & Welf, Dept Publ Hlth Solut, Helsinki 00271, Finland.
    Kahonen, Mika
    Tampere Univ Hosp, Dept Clin Physiol, Tampere 33522, Finland;Tampere Univ, Fac Med & Hlth Technol, Finnish Cardiovasc Res Ctr Tampere, Dept Clin Physiol, Tampere 33522, Finland.
    Kizer, Jorge R.
    Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA;Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA.
    Kovacs, Peter
    Univ Leipzig, Med Dept Endocrinol Nephrol Rheumatol 3, Leipzig, Germany.
    Kriebel, Jennifer
    Helmholtz Zentrum Munchen, Res Ctr Environm Hlth, Inst Epidemiol, Res Unit Mol Epidemiol, D-85764 Munich, Germany;German Ctr Diabet Res, D-85765 Munich, Germany.
    Laakso, Markku
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio 70029, Kys, Finland;Kuopio Univ Hosp, Kuopio 70029, Kys, Finland.
    Lange, Leslie A.
    Univ Colorado, Dept Med, Div Biomed Informat & Personalized Med, Denver, CO 80045 USA.
    Lehtimaki, Terho
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland;Tampere Univ, Fac Med & Hlth Technol, Finnish Cardiovasc Res Ctr Tampere, Dept Clin Chem, Tampere 33522, Finland.
    Li, Jin
    Stanford Univ, Dept Med, Div Cardiovasc Med, Palo Alto, CA 94304 USA.
    Li-Gao, Ruifang
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Luan, Jian'an
    Univ Cambridge, MRC Epidemiol Unit, Cambridge CB2 0QQ, England.
    Lyytikainen, Leo-Pekka
    Fimlab Labs, Dept Clin Chem, Tampere 33522, Finland;Tampere Univ, Fac Med & Hlth Technol, Finnish Cardiovasc Res Ctr Tampere, Dept Clin Chem, Tampere 33521, Finland.
    MacGregor, Stuart
    QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia.
    Mackey, David A.
    Univ Western Australia, Fac Hlth & Med Sci, Perth, WA 6009, Australia;Univ Western Australia, Lions Eye Inst, Ctr Ophthalmol & Visual Sci, Perth, WA 6009, Australia.
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7FZ, England;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7FZ, England.
    Mangino, Massimo
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England;Guys & St Thomas Fdn Trust, NIHR Biomed Res Ctr, London SE1 9RT, England.
    Mannisto, Satu
    Natl Inst Hlth & Welf, Dept Publ Hlth Solut, Helsinki 00271, Finland.
    McCarthy, Mark I.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7FZ, England;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7FZ, England;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford OX3 7FZ, England.
    McKnight, Barbara
    Univ Washington, Dept Biostat, Seattle, WA 98101 USA.
    Medina-Gomez, Carolina
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands.
    Meigs, James B.
    Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA;Harvard Med Sch, Dept Med, Boston, MA 02115 USA;Broad Inst, Program Populat & Med Genet, Cambridge, MA 02114 USA.
    Molnos, Sophie
    Helmholtz Zentrum Munchen, Res Ctr Environm Hlth, Inst Epidemiol, Res Unit Mol Epidemiol, D-85764 Munich, Germany;German Ctr Diabet Res, D-85765 Munich, Germany.
    Mook-Kanamori, Dennis
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2333 ZA Leiden, Netherlands;Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, NL-2334 ZA Leiden, Netherlands.
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7FZ, England;Univ Liverpool, Dept Biostat, Liverpool L69 3GL, Merseyside, England.
    de Mutsert, Renee
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2333 ZA Leiden, Netherlands.
    Nalls, Mike A.
    NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA;Data Tecn Int, Glen Echo, MD 20812 USA.
    Nedeljkovic, Ivana
    Erasmus MC, Dept Epidemiol, NL-3015 CN Rotterdam, Netherlands.
    North, Kari E.
    Univ North Carolina Chapel Hill, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA.
    Pennell, Craig E.
    Univ Newcastle, Sch Med & Publ Hlth, Fac Med & Hlth, Newcastle, NSW 2305, Australia.
    Pradhan, Aruna D.
    Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA;Harvard Med Sch, Boston, MA 02115 USA.
    Province, Michael A.
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.
    Raitakari, Olli T.
    Univ Turku, Ctr Populat Hlth Res, Turku, Finland;Turku Univ Hosp, Turku, Finland;Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland;Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku, Finland.
    Raulerson, Chelsea K.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
    Reiner, Alex P.
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
    Ridker, Paul M.
    Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA;Harvard Med Sch, Boston, MA 02115 USA.
    Ripatti, Samuli
    Broad Inst MIT & Harvard, Cambridge, MA 02142 USA;Univ Helsinki, Publ Hlth, FIN-00014 Helsinki, Finland;Inst Mol Med Finland, Helsinki 00014, Finland.
    Roberston, Neil
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7FZ, England;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7FZ, England.
    Rotter, Jerome I.
    Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Dept Publ Hlth Solut, Helsinki 00271, Finland.
    Sandoval-Zarate, America A.
    Inst Mol Med Finland, Helsinki 00014, Finland.
    Sitlani, Colleen M.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA.
    Spector, Tim D.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England.
    Strauch, Konstantin
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Genet Epidemiol, D-85764 Neuherberg, Germany;Ludwig Maximilians Univ Munchen, Inst Med Informat Biometry & Epidemiol, Chair Genet Epidemiol, D-81377 Munich, Germany.
    Stumvoll, Michael
    Univ Leipzig, Med Dept Endocrinol Nephrol Rheumatol 3, Leipzig, Germany.
    Taylor, Kent D.
    Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.
    Thuesen, Betina
    Capital Reg, Bispebjerg & Frederiksberg Hosp, Ctr Clin Res & Dis Prevent, DK-2400 Copenhagen, Denmark.
    Toenjes, Anke
    Univ Leipzig, Med Dept Endocrinol Nephrol Rheumatol 3, Leipzig, Germany.
    Uitterlinden, Andre G.
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands.
    Venturini, Cristina
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England.
    Walker, Mark
    Newcastle Univ, Sch Med, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England.
    Wang, Carol A.
    Univ Newcastle, Sch Med & Publ Hlth, Fac Med & Hlth, Newcastle, NSW 2305, Australia.
    Wang, Shuai
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
    Wareham, Nicholas J.
    Univ Cambridge, MRC Epidemiol Unit, Cambridge CB2 0QQ, England.
    Willems, Sara M.
    Univ Cambridge, MRC Epidemiol Unit, Cambridge CB2 0QQ, England.
    van Dijk, Ko Willems
    Leiden Univ, Med Ctr, Div Endocrinol, Dept Internal Med, NL-2333 ZA Leiden, Netherlands;Einthoven Lab Expt Vasc Med, NL-2333 ZA Leiden, Netherlands;Leiden Univ, Med Ctr, Dept Human Genet, NL-2333 ZA Leiden, Netherlands.
    Wilson, James G.
    Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
    Wu, Ying
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
    Yao, Jie
    Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.
    Young, Kristin L.
    Univ North Carolina Chapel Hill, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA.
    Langenberg, Claudia
    Univ Cambridge, MRC Epidemiol Unit, Cambridge CB2 0QQ, England.
    Frayling, Timothy M.
    Univ Exeter, Sch Med, Royal Devon & Exeter Hosp, Genet Complex Traits, Exeter EX2 5DW, Devon, England.
    Kilpelainen, Tuomas O.
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2200 Copenhagen, Denmark;Icahn Sch Med Mt Sinai, Dept Environm Med & Publ Hlth, New York, NY 10029 USA.
    Lindgren, Cecilia M.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7FZ, England;Broad Inst MIT & Harvard, Cambridge, MA 02142 USA;Univ Oxford, Nuffield Dept Med, Big Data Inst, Oxford OX3 7LF, England.
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA.
    Mohlke, Karen L.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
    Exome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology2019Inngår i: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 105, nr 1, s. 15-28Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Circulating levels of adiponectin, an adipocyte-secreted protein associated with cardiovascular and metabolic risk, are highly heritable. To gain insights into the biology that regulates adiponectin levels, we performed an exome array meta-analysis of 265,780 genetic variants in 67,739 individuals of European, Hispanic, African American, and East Asian ancestry. We identified 20 loci associated with adiponectin, including 11 that had been reported previously (p < 2 x 10(-7)). Comparison of exome array variants to regional linkage disequilibrium (LD) patterns and prior genome-wide association study (GWAS) results detected candidate variants (r(2) > .60) spanning as much as 900 kb. To identify potential genes and mechanisms through which the previously unreported association signals act to affect adiponectin levels, we assessed cross-trait associations, expression quantitative trait loci in subcutaneous adipose, and biological pathways of nearby genes. Eight of the nine loci were also associated (p < 1 x 10(-4)) with at least one obesity or lipid trait. Candidate genes include PRKAR2A, PTH1R, and HDAC9, which have been suggested to play roles in adipocyte differentiation or bone marrow adipose tissue. Taken together, these findings provide further insights into the processes that influence circulating adiponectin levels.

  • 275.
    Stenemo, M. Markus
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala Univ, Dept Med Sci, Uppsala, Sweden..
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Proteomic profiling and the risk of heart failure2015Inngår i: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 17, s. 141-141Artikkel i tidsskrift (Annet vitenskapelig)
  • 276.
    Stenemo, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Molecular Epidemiology of Cardiovascular Disease2019Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Cardiovascular disease is a major cause of morbidity and mortality, with increasing prevalence worldwide.

    Identification of risk markers may enable improved prevention by targeting high-risk individuals, earlier disease diagnosis and treatment, as well as stratification of disease subtypes with different treatment options, thereby minimizing side effects while increasing success rates.

    The overall aim of this thesis was to investigate associations between proteomic and metabolomic biomarkers, and the development of heart failure and ischemic stroke. Specific objectives were to examine potential causal pathways, and the added value in risk prediction of the identified risk markers.

    In Studies I–II, we performed proximity extension assay based proteomic profiling of ≥80 circulating proteins in the Swedish cohorts Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS n=901, median age 70), and the Uppsala Longitudinal Study of Adult Men (ULSAM, n=685, median age 77). In Study I, we identified nine proteins involved in apoptosis, inflammation, matrix remodeling, and fibrinolysis associated with incident heart failure, including growth differentiation factor-15 (GDF-15). In Study II, we identified several proteins associated with incident ischemic stroke, including GDF-15. Both studies revealed potential to improve disease risk prediction by using proteomic data.

    In Study III, we performed mass spectrometry-based metabolomic profiling in plasma or serum samples from PIVUS, ULSAM, and TwinGene (total n=3,924). The metabolites urobilin and sphingomyelin (30:1) were associated with incident heart failure.

    In Study IV, we followed up on the results of Studies I–II, performing Mendelian randomization analyses (a framework for causal analysis using genetic variants) in 1,053,527 individuals, with 88,448 coronary artery disease cases, 70,305 ischemic stroke cases, and 1,420 heart failure cases. This study supports a causal role of genetically elevated GDF-15 levels in heart failure development, but not in coronary artery disease or ischemic stroke.

    In conclusion, we identified multiple biomarkers associated with incident heart failure and ischemic stroke, potentially involved in early disease development. We also saw potential to improve disease risk prediction for incident heart failure and ischemic stroke using proteomics data.

    Our findings encourage further large-scale proteomic, metabolomic, and genetic studies to give new insights into heart failure and stroke pathogenesis.

    Delarbeid
    1. Circulating proteins as predictors of incident heart failure in the elderly
    Åpne denne publikasjonen i ny fane eller vindu >>Circulating proteins as predictors of incident heart failure in the elderly
    Vise andre…
    2018 (engelsk)Inngår i: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 20, nr 1, s. 55-62Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Aims

    To identify novel risk markers for incident heart failure using proteomic profiling of 80 proteins previously associated with cardiovascular pathology.

    Methods and results

    Proteomic profiling (proximity extension assay) was performed in two community‐based prospective cohorts of elderly individuals without heart failure at baseline: the Prospective Investigation of the Vasculature in Uppsala Seniors [PIVUS, n = 901, median age 70.2 (interquartile range 70.0–70.3) years, 80 events]; and the Uppsala Longitudinal Study of Adult Men [ULSAM, n = 685, median age 77.8 (interquartile range 76.9–78.1) years, 90 events]. Twenty‐nine proteins were associated with incident heart failure in the discovery cohort PIVUS after adjustment for age and sex, and correction for multiple testing. Eighteen associations replicated in ULSAM. In pooled analysis of both cohorts, higher levels of nine proteins were associated with incident heart failure after adjustment for established risk factors: growth differentiation factor 15 (GDF‐15), T‐cell immunoglobulin and mucin domain 1 (TIM‐1), tumour necrosis factor‐related apoptosis‐inducing ligand receptor 2 (TRAIL‐R2), spondin‐1 (SPON1), matrix metalloproteinase‐12 (MMP‐12), follistatin (FS), urokinase‐type plasminogen activator surface receptor (U‐PAR), osteoprotegerin (OPG), and suppression of tumorigenicity 2 (ST2). Of these, GDF‐15, U‐PAR, MMP‐12, TRAIL‐R2, SPON1 and FS were associated with worsened echocardiographic left ventricular systolic function at baseline, while only TIM‐1 was positively associated with worsened diastolic function (P < 0.02 for all).

    Conclusion

    Proteomic profiling identified several novel associations between proteins involved in apoptosis, inflammation, matrix remodelling, and fibrinolysis with incident heart failure in elderly individuals. Our results encourage additional studies investigating the underlying mechanisms and the clinical utility of our findings.

    Emneord
    Biomarkers, Epidemiology, Heart failure, Left ventricular dysfunction, Proteomics, Risk prediction
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-334416 (URN)10.1002/ejhf.980 (DOI)000423809700007 ()28967680 (PubMedID)
    Forskningsfinansiär
    EU, Horizon 2020, 634869Swedish Research Council, 2012-2215; 2015-03477; 221-2013-1673Marianne and Marcus Wallenberg Foundation, 2012.0082Swedish Heart Lung Foundation, 20140422; 20150429; 20120169Knut and Alice Wallenberg Foundation, 2013.0126Göran Gustafsson Foundation for promotion of scientific research at Uppala University and Royal Institute of Technology, 1637
    Merknad

    Tove Fall och Johan Ärnlöv delar på sistaförfattarskapet.

    Tilgjengelig fra: 2017-11-23 Laget: 2017-11-23 Sist oppdatert: 2019-04-09bibliografisk kontrollert
    2. Discovery of New Risk Markers for Ischemic Stroke Using a Novel Targeted Proteomics Chip
    Åpne denne publikasjonen i ny fane eller vindu >>Discovery of New Risk Markers for Ischemic Stroke Using a Novel Targeted Proteomics Chip
    Vise andre…
    2015 (engelsk)Inngår i: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 46, nr 12, s. 3340-3347Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Background and Purpose-Emerging technologies have made it possible to simultaneously evaluate a large number of circulating proteins as potential new stroke risk markers. Methods-We explored associations between 85 cardiovascular proteins, assessed by a proteomics chip, and incident ischemic stroke in 2 independent cohorts of elderly (Prospective Investigation of the Vasculature in Uppsala Seniors [PIVUS]: n=977; 50% women, mean age=70.1 years, 71 fatal/nonfatal ischemic stroke events during 10.0 years; and Uppsala Longitudinal Study in Adult Men [ULSAM]: n=720, mean age=77.5 years, 75 ischemic stroke events during 9.5 years). The proteomics chip uses 2 antibodies for each protein and a polymerase chain reaction step to achieve a high-specific binding and the possibility to measure multiple proteins in parallel, but gives no absolute concentrations. Results-In PIVUS, 16 proteins were related to incident ischemic stroke using a false discovery rate of 5%. Of these, N-terminal pro-B-type natriuretic peptide (P=0.0032), adrenomedullin (P=0.018), and eosinophil cationic protein (P=0.0071) were replicated in ULSAM after adjustment for established stroke risk factors. In predefined secondary meta-analyses of individual data, interleukin-27 subunit , growth/differentiation factor 15, urokinase plasminogen activator surface receptor, tumor necrosis factor receptor superfamily member 6, macrophage colony-stimulating factor 1, and matrix metalloproteinase-7 were also potential risk markers for ischemic stroke after adjustment for multiple comparisons (P<0.0006). The addition of N-terminal pro-B-type natriuretic peptide, adrenomedullin, and eosinophil cationic protein to a model with established risk factors increased the C-statistic from 0.629 to 0.689 (P=0.001). Conclusions-Our data suggest that large-scale proteomics analysis is a promising way of discovering novel biomarkers that could substantially improve the prediction of ischemic stroke.

    Emneord
    adrenomedullin, natriuretic peptide, brain, proteins, risk factors, stroke
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-270960 (URN)10.1161/STROKEAHA.115.010829 (DOI)000365534400001 ()26542692 (PubMedID)
    Forskningsfinansiär
    AstraZenecaEU, European Research Council, 634869Swedish Research Council, 2012-1727Swedish Research Council, 2012-2215Swedish Heart Lung FoundationMarianne and Marcus Wallenberg Foundation
    Tilgjengelig fra: 2016-01-05 Laget: 2016-01-05 Sist oppdatert: 2019-04-09bibliografisk kontrollert
    3. The metabolites urobilin and sphingomyelin (30:1) are associated with incident heart failure in the general population
    Åpne denne publikasjonen i ny fane eller vindu >>The metabolites urobilin and sphingomyelin (30:1) are associated with incident heart failure in the general population
    Vise andre…
    2019 (engelsk)Inngår i: ESC Heart Failure, E-ISSN 2055-5822, Vol. 6, nr 4, s. 764-773Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Aims: We aimed to investigate whether metabolomic profiling of blood can lead to novel insights into heart failure pathogenesis or improved risk prediction.

    Methods: Mass spectrometry-based metabolomic profiling was performed in plasma or serum samples from three community-based cohorts without heart failure at baseline (total n=3,924; 341 incident heart failure events, median follow-up ranging from 4.6 to 13.9 years). Cox proportional hazards models were applied to assess the association of each of the 206 identified metabolites with incident heart failure in the discovery cohorts Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS, n=920) and Uppsala Longitudinal Study of Adult Men (ULSAM, n=1,121). Replication was undertaken in the independent cohort TwinGene (n=1,797). We also assessed whether metabolites could improve the prediction of heart failure beyond established risk factors (age, sex, body mass index, low-density lipoprotein- and high-density lipoprotein-cholesterol, triglycerides, lipid medication, diabetes, systolic and diastolic blood pressure, blood pressure medication, glomerular filtration rate, smoking status, and myocardial infarction prior to or during follow-up).

    Results: Higher circulating urobilin and lower sphingomyelin (30:1) were associated with incident heart failure in age- and sex-adjusted models in the discovery and replication sample. The hazard ratio (HR) for urobilin in the replication cohort was estimated to 1.29 per SD unit, 95% confidence interval (CI) 1.03-1.63) and for sphingomyelin (30:1) to 0.72 (95% CI 0.58-0.89). Results remained similar after further adjustment for established heart failure risk factors in meta-analyses of all three cohorts. Urobilin concentrations were inversely associated with left ventricular ejection fraction at baseline in the PIVUS cohort (β= -0.70 (95% CI -1.03-(-0.38)). No improvement in risk prediction was observed when adding the two top metabolites (C-index 0.787 (95% CI 0.752-0.823)) or nine Lasso-selected metabolites (0.790 (95% CI 0.754-0.826)) to a modified Atherosclerosis Risk in Communities (ARIC) heart failure risk score model (0.780 (95% CI 0.745-0.816)).

    Conclusions: Our metabolomics study identified associations of circulating levels of the heme breakdown product urobilin, and sphingomyelin (30:1), a cell membrane component involved in signal transduction and apoptosis, with incident heart failure.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-381229 (URN)10.1002/ehf2.12453 (DOI)000478602300020 ()31148414 (PubMedID)
    Forskningsfinansiär
    Swedish Research Council, 2017-00641Swedish Research Council, 2012-02215Swedish Heart Lung FoundationEU, Horizon 2020, 634869
    Tilgjengelig fra: 2019-04-05 Laget: 2019-04-05 Sist oppdatert: 2019-09-24bibliografisk kontrollert
    4. The role of growth differentiation factor 15 (GDF-15) in cardiovascular disease – a Mendelian Randomization study
    Åpne denne publikasjonen i ny fane eller vindu >>The role of growth differentiation factor 15 (GDF-15) in cardiovascular disease – a Mendelian Randomization study
    (engelsk)Inngår i: Artikkel i tidsskrift (Annet vitenskapelig) Submitted
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-381231 (URN)
    Tilgjengelig fra: 2019-04-05 Laget: 2019-04-05 Sist oppdatert: 2019-04-09
  • 277.
    Stenemo, Markus
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Ganna, Andrea
    Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA ; Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA ; Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA ; Karolinska Inst, Dept Med Epidemiol & Biostat MEB, Stockholm, Sweden.
    Salihovic, Samira
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Nowak, Christoph
    Karolinska Inst, Dept Neurobiol Care Sci & Soc NVS, Div Family Med & Primary Care, Stockholm, Sweden.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi. George Inst Global Hlth, Sydney, NSW, Australia.
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Broeckling, Corey
    Colorado State Univ, Prote & Metabol Facil, Ft Collins, CO 80523 USA.
    Prenni, Jessica
    Colorado State Univ, Prote & Metabol Facil, Ft Collins, CO 80523 USA ; Colorado State Univ, Dept Hort & Landscape Architecture, Ft Collins, CO 80523 USA.
    Svensson, Per
    Karolinska Inst, Dept Clin Sci & Educ, Dept Cardiol, Sodersjukhuset, Stockholm, Sweden.
    Magnusson, Patrik
    Karolinska Inst, Dept Med Epidemiol & Biostat MEB, Stockholm, Sweden.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA ; Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA ; Stanford Univ, Stanford Diabet Res Ctr, Stanford, CA 94305 USA.
    Ärnlöv, Johan
    Karolinska Inst, Dept Neurobiol Care Sci & Soc NVS, Div Family Med & Primary Care, Stockholm, Sweden ; Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden.
    Fall, Tove
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    The metabolites urobilin and sphingomyelin (30:1) are associated with incident heart failure in the general population2019Inngår i: ESC Heart Failure, E-ISSN 2055-5822, Vol. 6, nr 4, s. 764-773Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims: We aimed to investigate whether metabolomic profiling of blood can lead to novel insights into heart failure pathogenesis or improved risk prediction.

    Methods: Mass spectrometry-based metabolomic profiling was performed in plasma or serum samples from three community-based cohorts without heart failure at baseline (total n=3,924; 341 incident heart failure events, median follow-up ranging from 4.6 to 13.9 years). Cox proportional hazards models were applied to assess the association of each of the 206 identified metabolites with incident heart failure in the discovery cohorts Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS, n=920) and Uppsala Longitudinal Study of Adult Men (ULSAM, n=1,121). Replication was undertaken in the independent cohort TwinGene (n=1,797). We also assessed whether metabolites could improve the prediction of heart failure beyond established risk factors (age, sex, body mass index, low-density lipoprotein- and high-density lipoprotein-cholesterol, triglycerides, lipid medication, diabetes, systolic and diastolic blood pressure, blood pressure medication, glomerular filtration rate, smoking status, and myocardial infarction prior to or during follow-up).

    Results: Higher circulating urobilin and lower sphingomyelin (30:1) were associated with incident heart failure in age- and sex-adjusted models in the discovery and replication sample. The hazard ratio (HR) for urobilin in the replication cohort was estimated to 1.29 per SD unit, 95% confidence interval (CI) 1.03-1.63) and for sphingomyelin (30:1) to 0.72 (95% CI 0.58-0.89). Results remained similar after further adjustment for established heart failure risk factors in meta-analyses of all three cohorts. Urobilin concentrations were inversely associated with left ventricular ejection fraction at baseline in the PIVUS cohort (β= -0.70 (95% CI -1.03-(-0.38)). No improvement in risk prediction was observed when adding the two top metabolites (C-index 0.787 (95% CI 0.752-0.823)) or nine Lasso-selected metabolites (0.790 (95% CI 0.754-0.826)) to a modified Atherosclerosis Risk in Communities (ARIC) heart failure risk score model (0.780 (95% CI 0.745-0.816)).

    Conclusions: Our metabolomics study identified associations of circulating levels of the heme breakdown product urobilin, and sphingomyelin (30:1), a cell membrane component involved in signal transduction and apoptosis, with incident heart failure.

  • 278.
    Stenemo, Markus
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Nowak, Christoph
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Stanford University School of Medicine, Department of Medicine, Division of Cardiovascular Medicine.
    Fall, Tove
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Ärnlöv, Johan
    Dalarna University, School of Health and Social Studies, Falun; Karolinska Institutet, Care Science and Society, Department of Neurobiology, Division of Family Medicine and Primary Care .
    Circulating proteins as predictors of incident heart failure in the elderly2018Inngår i: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 20, nr 1, s. 55-62Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims

    To identify novel risk markers for incident heart failure using proteomic profiling of 80 proteins previously associated with cardiovascular pathology.

    Methods and results

    Proteomic profiling (proximity extension assay) was performed in two community‐based prospective cohorts of elderly individuals without heart failure at baseline: the Prospective Investigation of the Vasculature in Uppsala Seniors [PIVUS, n = 901, median age 70.2 (interquartile range 70.0–70.3) years, 80 events]; and the Uppsala Longitudinal Study of Adult Men [ULSAM, n = 685, median age 77.8 (interquartile range 76.9–78.1) years, 90 events]. Twenty‐nine proteins were associated with incident heart failure in the discovery cohort PIVUS after adjustment for age and sex, and correction for multiple testing. Eighteen associations replicated in ULSAM. In pooled analysis of both cohorts, higher levels of nine proteins were associated with incident heart failure after adjustment for established risk factors: growth differentiation factor 15 (GDF‐15), T‐cell immunoglobulin and mucin domain 1 (TIM‐1), tumour necrosis factor‐related apoptosis‐inducing ligand receptor 2 (TRAIL‐R2), spondin‐1 (SPON1), matrix metalloproteinase‐12 (MMP‐12), follistatin (FS), urokinase‐type plasminogen activator surface receptor (U‐PAR), osteoprotegerin (OPG), and suppression of tumorigenicity 2 (ST2). Of these, GDF‐15, U‐PAR, MMP‐12, TRAIL‐R2, SPON1 and FS were associated with worsened echocardiographic left ventricular systolic function at baseline, while only TIM‐1 was positively associated with worsened diastolic function (P < 0.02 for all).

    Conclusion

    Proteomic profiling identified several novel associations between proteins involved in apoptosis, inflammation, matrix remodelling, and fibrinolysis with incident heart failure in elderly individuals. Our results encourage additional studies investigating the underlying mechanisms and the clinical utility of our findings.

  • 279.
    Stojkovic, Stefan
    et al.
    Med Univ Vienna, Dept Internal Med 2, Vienna, Austria..
    Thulin, Åsa
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap.
    Hell, Lena
    Med Univ Vienna, Dept Internal Med 1, Clin Div Hematol & Hemostaseol, Vienna, Austria..
    Thaler, Barbara
    Med Univ Vienna, Dept Internal Med 2, Vienna, Austria..
    Rauscher, Sabine
    Med Univ Vienna, Core Facil, Vienna, Austria..
    Baumgartner, Johanna
    Med Univ Vienna, Dept Internal Med 2, Vienna, Austria..
    Groeger, Marion
    Med Univ Vienna, Core Facil, Vienna, Austria..
    Ay, Cihan
    Med Univ Vienna, Dept Internal Med 1, Clin Div Hematol & Hemostaseol, Vienna, Austria..
    Demyanets, Svitlana
    Med Univ Vienna, Dept Lab Med, Vienna, Austria..
    Neumayer, Christoph
    Med Univ Vienna, Dept Surg, Div Vasc Surg, Vienna, Austria..
    Huk, Ihor
    Med Univ Vienna, Dept Surg, Div Vasc Surg, Vienna, Austria..
    Spittler, Andreas
    Med Univ Vienna, Core Facil, Vienna, Austria.;Med Univ Vienna, Dept Surg, Div Vasc Surg, Vienna, Austria..
    Huber, Kurt
    Wilhelminen Hosp, Med Dept Cardiol & Emergency Med 3, Vienna, Austria.;Sigmund FReud Private Univ, Med Sch, Vienna, Austria..
    Wojta, Johann
    Med Univ Vienna, Dept Internal Med 2, Vienna, Austria.;Med Univ Vienna, Core Facil, Vienna, Austria.;Sigmund FReud Private Univ, Med Sch, Vienna, Austria.;Ludwig Boltzmann Cluster Cardiovascular Res, Vienna, Austria..
    Siegbahn, Agneta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Åberg, Mikael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    IL-33 stimulates the release of procoagulant microvesicles from human monocytes and differentially increases tissue factor in human monocyte subsets2017Inngår i: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 117, nr 7, s. 1379-1390Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Monocytes and monocyte-derived microvesicles (MVs) are the main source of circulating tissue factor (TF). Increased monocyte TF expression and increased circulating levels of procoagulant MVs contribute to the formation of a prothrombotic state in patients with cardiovascular disease. Interleukin (IL)-33 is a pro-inflammatory cytokine involved in atherosclerosis and other inflammatory diseases, but its role in regulating thrombosis is still unclear. The aim of the present study was to investigate the effects of IL-33 on the procoagulant properties of human monocytes and monocyte-derived MVs. IL-33 induced a time- and concentration-dependent increase of monocyte TF mRNA and protein levels via binding to the ST2-receptor and activation of the NF-kappa B-pathway. The IL-33 treated monocytes also released CD14+TF+ MVs and IL-33 was found to increase the TF activity of both the isolated monocytes and monocyte-derived MVs. The monocytes were classified into subsets according to their CD14 and CD16 expression. Intermediate monocytes (IM) showed the highest ST2 receptor expression, followed by non-classical monocytes (NCM), and classical monocytes (CM). IL-33 induced a significant increase of TF only in the IM (p<0.01), with a tendency in NCM (p=0.06), but no increase was observed in CM. Finally, plasma levels of IL-33 were positively correlated with CD14+TF+ MVs in patients undergoing carotid endarterectomy (r=0.480; p=0.032; n=20). We hereby provide novel evidence that the proinflammatory cytokine IL-33 induces differential TF expression and activity in monocyte subsets, as well as the release of procoagulant MVs. In this manner, IL-33 may contribute to the formation of a prothrombotic state characteristic for cardiovascular disease.

  • 280. Strage, E. M.
    et al.
    Lewitt, M. S.
    Hanson, J. M.
    Olsson, U.
    Norrvik, F.
    Lilliehook, I.
    Holst, B. S.
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Relationship among Insulin Resistance, Growth Hormone, and Insulin-Like Growth Factor I Concentrations in Diestrous Swedish Elkhounds2014Inngår i: Journal of Veterinary Internal Medicine, ISSN 0891-6640, E-ISSN 1939-1676, Vol. 28, nr 2, s. 419-428Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background In the dog, the normal estrous cycle includes a prolonged luteal phase. Progesterone stimulates local canine mammary growth hormone (GH) production, which may act systemically and contribute to insulin resistance. Swedish Elkhounds are predisposed to progesterone-related diabetes mellitus, and the relationship among insulin resistance, GH, and insulin-like growth factor I (IGF-I) is of particular interest. Objective To study insulin resistance in relation to GH and IGF-I in nondiabetic Swedish Elkhounds during diestrus. We also assessed whether alterations in these hormones could predict diestrus-linked diseases and all-cause mortality. Animals Eighty-four privately owned female intact Swedish Elkhounds >4years of age. Methods Blood sampling and clinical examination during luteal phase, with a follow-up questionnaire after 20months. Insulin resistance was calculated by homeostasis model assessment (HOMA-IR). Results In multivariable regression analysis, GH was positively associated with HOMA-IR (P=.009). An increase in GH of 1ng/mL was associated with a 12.7% increase in HOMA-IR. Moreover, C-peptide was positively associated with IGF-I (P=.04), and an increase in C-peptide of 0.1ng/mL was associated with a 6.9% increase in IGF-I. Structural equation modeling supported these results. Twenty-three animals were found to have previously unrecognized mammary masses and had higher GH (P<.0001) and IGF-I (P=.007) than dogs without mammary masses (n=61). There was no association between high GH and IGF-I concentrations at sampling and future mammary masses. Conclusion We showed that GH was strongly associated with insulin resistance in older Swedish Elkhounds during diestrus.

  • 281. Strage, Emma M
    et al.
    Sundberg, Mårten
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Holst, Bodil S
    Andersson Franko, Mikael
    Ramström, Margareta
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Fall, Tove
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Lewitt, Moira
    Effect of insulin treatment on circulating insulin-like growth factor I and IGF-binding proteins in cats with diabetes mellitus.2018Inngår i: Journal of Veterinary Internal Medicine, ISSN 0891-6640, E-ISSN 1939-1676, Vol. 32, nr 5, s. 1579-1590Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Insulin-like growth factor-I (IGF-I) is used to screen for acromegaly in diabetic cats. In humans, most circulating IGF-I forms ternary complexes (TC) with IGF-binding protein (IGFBP-3) and an acid-labile subunit. Compared to humans, the amount of TC in cats is more variable. Insulin-like growth factor-I concentrations are reported to increase during insulin treatment, more rapidly in cats achieving remission.

    OBJECTIVES: To investigate (i) factors associated with circulating IGF-I concentrations, including IGFBP-profiles (ii) effect of insulin treatment on IGF-I concentrations and (iii) IGF-I as prognostic marker of diabetes mellitus remission.

    ANIMALS: Thirty-one privately owned diabetic cats of which 24 were followed 1 year, and 13 healthy cats.

    METHODS: Prospective study. Serum insulin, IGF-I, glucose, and fructosamine concentrations were measured. IGF-binding forms were determined by chromatography in 14 diabetic and 13 healthy cats; and IGF-I, IGF-II, IGFBP-3, and IGFBP-5 by mass spectrometry in 3 cats achieving remission.

    RESULTS: Insulin-like growth factor-I median (interquartile range) before start of insulin treatment was 300 (160-556) ng/mL. Insulin-like growth factor-I was positively associated with TC (P < .0001) and endogenous insulin (P = .005) and negatively associated with fructosamine (P < .0001). Median IGF-I was higher 2-4 weeks after start of insulin treatment compared with baseline (300 versus 670 ng/mL, P = .0001) and predicted future remission (P = .046). In cats that went into remission, the amount of TC and IGFBP-3 increased, suggesting increase in IGF-I is dependent on TC formation.

    CONCLUSIONS: Insulin treatment should be accounted for when interpreting IGF-I in diabetic cats. Insulin-like growth factor-I 2-4 weeks after initiation of insulin treatment shows promise as prognostic marker for remission in diabetic cats.

  • 282.
    Strawbridge, Rona J.
    et al.
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden.;Univ Glasgow, Inst Mental Hlth & Wellbeing, Mental Hlth & Wellbeing, Glasgow, Lanark, Scotland.;Univ Glasgow, Dept Hlth & Wellbeing, Glasgow G12 8RZ, Lanark, Scotland..
    Silveira, Angela
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden..
    den Hoed, Marcel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Gustafsson, Stefan
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Luan, Jian'an
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge, England..
    Rybin, Denis
    Boston Univ, Data Coordinating Ctr, Boston, MA 02215 USA..
    Dupuis, Josee
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.;Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA..
    Li-Gao, Ruifang
    Leiden Univ, Dept Clin Epidemiol, Med Ctr, Leiden, Netherlands..
    Kavousi, Maryam
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Dehghan, Abbas
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, London, England..
    Haljas, Kadri
    Univ Helsinki, Fac Med, Dept Psychol & Logoped, Helsinki, Finland..
    Lahti, Jari
    Univ Helsinki, Fac Med, Dept Psychol & Logoped, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland..
    Gadin, Jesper R.
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden..
    Backlund, Alexandra
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden..
    de Faire, Ulf
    Karolinska Inst, Inst Environm Med, Div Cardiovasc Epidemiol, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden..
    Gertow, Karl
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden..
    Giral, Phillipe
    Grp Hosp Pitie Salpetriere, AP HP, Serv Endocrinol Metab, Unites Prevent Cardiovasc, Paris, France..
    Goel, Anuj
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Div Cardiovasc Med, Oxford, England..
    Humphries, Steve E.
    UCL, Inst Cardiovasc Sci, Ctr Cardiovasc Genet, London, England..
    Kurl, Sudhir
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio Campus, Kuopio, Finland..
    Langenberg, Claudia
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge, England.;Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, London, England..
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge, England.;Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, London, England..
    Lindgren, Cecilia C. M.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Mannarino, Elmo
    Univ Perugia, Dept Clin & Expt Med Internal Med Angiol & Arteri, Perugia, Italy..
    Mook-Kanamori, Dennis O.
    Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, Leiden, Netherlands..
    Morris, Andrew P.
    Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England..
    de Mutsert, Renee
    Univ Helsinki, Fac Med, Dept Psychol & Logoped, Helsinki, Finland..
    Rauramaa, Rainer
    Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio, Finland.;Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, Kuopio, Finland..
    Saliba-Gustafsson, Peter
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden..
    Sennblad, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär evolution. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden.
    Smit, Andries J.
    Univ Med Ctr Groningen, Dept Med, Groningen, Netherlands.;Univ Groningen, Univ Med Ctr Groningen, Dept Med, Groningen, Netherlands..
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Tremoli, Elena
    Univ Milan, Dipartimento Sci Farmacolog & Biomol, Milan, Italy.;IRCCS, Ctr Cardiolog Monzino, Milan, Italy..
    Veglia, Fabrizio
    IRCCS, Ctr Cardiolog Monzino, Milan, Italy..
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Bjorck, Hanna M.
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden..
    Eriksson, Johan G.
    Folkhalsan Res Ctr, Helsinki, Finland.;Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland.;Helsinki Univ Hosp, Helsinki, Finland.;Natl Inst Hlth & Welf, Helsinki, Finland..
    Hofman, Albert
    Harvard T H Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA..
    Franco, Oscar H.
    Watkins, Hugh
    Jukema, J. Wouter
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands.;Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands..
    Florez, Jose C.
    Massachusetts Gen Hosp, Diabet Unit, Boston, MA USA.;Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA USA.;Broad Inst, Programs Metab & Med & Populat Genet, Cambridge, MA USA.;Harvard Med Sch, Dept Med, Cambridge, MA USA..
    Wareham, Nicholas J.
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge, England..
    Meigs, James B.
    Broad Inst, Programs Metab & Med & Populat Genet, Cambridge, MA USA.;Harvard Med Sch, Dept Med, Cambridge, MA USA.;Massachusetts Gen Hosp, Gen Med Div, Boston, MA USA..
    Ingelsson, Erik
    Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Stanford, CA USA..
    Baldassarre, Damiano
    Univ Milan, Dipartimento Sci Farmacolog & Biomol, Milan, Italy.;Univ Milan, Dept Med Biotechnol & Translat Med, Milan, Italy..
    Hamsten, Anders
    Identification of a novel proinsulin-associated SNP and demonstration that proinsulin is unlikely to be a causal factor in subclinical vascular remodelling using Mendelian randomisation2017Inngår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 266, s. 196-204Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and aims: Increased proinsulin relative to insulin levels have been associated with subclinical atherosclerosis (measured by carotid intima-media thickness (cIMT)) and are predictive of future cardiovascular disease (CVD), independently of established risk factors. The mechanisms linking proinsulin to atherosclerosis and CVD are unclear. A genome-wide meta-analysis has identified nine loci associated with circulating proinsulin levels. Using proinsulin-associated SNPs, we set out to use a Mendelian randomisation approach to test the hypothesis that proinsulin plays a causal role in subclinical vascular remodelling.

    Methods: We studied the high CVD-risk IMPROVE cohort (n = 3345), which has detailed biochemical phenotyping and repeated, state-of-the-art, high-resolution carotid ultrasound examinations. Genotyping was performed using Illumina Cardio-Metabo and Immuno arrays, which include reported proinsulin-associated loci. Participants with type 2 diabetes (n = 904) were omitted from the analysis. Linear regression was used to identify proinsulin-associated genetic variants.

    Results: We identified a proinsulin locus on chromosome 15 (rs8029765) and replicated it in data from 20,003 additional individuals. An 11-SNP score, including the previously identified and the chromosome 15 proinsulin-associated loci, was significantly and negatively associated with baseline IMTmean and IMTmax (the primary cIMT phenotypes) but not with progression measures. However, MR-Eggers refuted any significant effect of the proinsulin-associated 11-SNP score, and a non-pleiotropic SNP score of three variants (including rs8029765) demonstrated no effect on baseline or progression cIMT measures.

    Conclusions: We identified a novel proinsulin-associated locus and demonstrated that whilst proinsulin levels are associated with cIMT measures, proinsulin per se is unlikely to have a causative effect on cIMT.

  • 283.
    Stubleski, Jordan
    et al.
    Örebro Univ, MTM Res Ctr, Sch Sci & Technol, Örebro, Sweden.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Salihovic, Samira
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Örebro Univ, MTM Res Ctr, Sch Sci & Technol, Örebro, Sweden.
    Lind, P. Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Kärrman, Anna
    Örebro Univ, MTM Res Ctr, Sch Sci & Technol, Örebro, Sweden.
    Longitudinal changes in persistent organic pollutants (POPs) from 2001 to 2009 in a sample of elderly Swedish men and women2018Inngår i: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 165, s. 193-200Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Prospective cohort studies evaluating the temporal trends of background-level persistent organic pollutants (POPs) and their potential negative health effects in humans are needed. Objective: The objectives of this study are to examine the five year longitudinal trend in chlorinated and bro-minated (Cl/Br) POP concentrations in a sample of elderly individuals and to investigate the relationship between gender, changes in body weight, plasma lipid levels and POP concentrations. Methods: In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, plasma samples were collected from the same individuals over a 5 year period. Originally 992 subjects (all aged 70) were sampled between 2001 and 2004 and 814 returning subjects (all aged 75) were sampled again from 2006 to 2009. Plasma concentrations of 16 polychlorinated biphenyls (PCBs), 5 organochlorine pesticides (OCPs), octachlorinated dibenzo-p-dioxin (OCDD), and one polybrominated diphenylether (BDE 47) were determined using high-throughput 96-well plate solid phase extraction and gas chromatography-high resolution mass spectrometry (GC-HAMS). Results: During the 5-year follow-up, plasma concentrations of all POPs significantly decreased (p < 0.00001). Median reductions ranged from 4% (PCB105) to 45% (PCB 99), with most reductions being in the 30-40% range. For most POPs, a larger decline was seen in men than in women. The relationship between the weight change and change in POP concentrations was generally negative, but a positive relationship between lipid levels and POP concentrations when expressed as wet-weight was observed. In general, similar changes in POP concentrations and their relationships to body weight were observed regardless of using either wet-weight (pg/ mL) or lipid-normalized (ng/g lipid) concentrations. Conclusion: In this longitudinal cohort study, gender and minor, but varying changes in body weight and lipid levels greatly influenced the individual-based changes in POP concentrations. In general, our findings suggest that men and women with larger decreases in body weight and greater increases in lipid levels have the slowest decline in body burden of POPs. Based on the results from this study, either wet-weight or lipid normalized concentrations can be used to determine the percent change in POP concentrations and their relationships to physiological changes and differences.

  • 284.
    Stubleski, Jordan
    et al.
    MTM Research Centre, School of Science and Technology, Örebro University, 70182 Örebro, Sweden.
    Salihovic, Samira
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Lind, P. Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    van Bavel, Bert
    MTM Research Centre, School of Science and Technology, Örebro University, 70182 Örebro, Sweden; Norwegian Institute for Water Research, NIVA, 0349 Oslo, Norway.
    Kärrman, Anna
    MTM Research Centre, School of Science and Technology, Örebro University, 70182 Örebro, Sweden.
    Changes in serum levels of perfluoroalkyl substances during a 10-year follow-up period in a large population-based cohort2016Inngår i: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 95, s. 86-92Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Poly- and perfluoroalkyl substances (PFASs) are a group of man-made fluorinated chemicals which have, at background levels, been associated with negative health effects in humans. Thus far, most human biomonitoring studies have evaluated the general change in PFAS concentration over time by continuously testing various individuals. This is one of the few studies to report the longitudinal trend of a range of PFAS concentrations in humans. In addition, this is the first known longitudinal study to include a large background level exposed cohort of both men and women with the same age and location who were repeatedly sampled from 2001 to 2014. The longitudinal change in concentration of eight PFASs detected in serum collected from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort were determined and compared to results from general population studies. The sex-dependent changes in PFAS concentrations over time were also assessed. Serum was sampled from the same individuals at ages 70 (collection period 2001-2004), 75 (2006-2009) and 80 (2011-2014,). Eight (C6-11) of fourteen (C4-13) analyzed PFASs were usually detected in over 75% of individuals and assessed using a random effects (mixed) model. In the 579 individuals attending all three examinations, PFOSA and PFOS concentrations significantly decreased, while the remaining six PFASs significantly increased between ages 70 and 75. However, between ages 75 and 80 all PFAS concentrations significantly decreased. Overall from age 70 to 80, concentrations of PFHxS, PFUnDA, PFNA, and PFDA showed a significant increase (7% to 34%), whereas concentrations of PFOSA, PFHpA, PFOS, and PFOA (-75% to -27%) significantly decreased. Over time PFHxS concentrations increased more among women, while PFHpA concentrations showed a greater decrease among men. From age 70 to age 80, spanning from 2001-2004 to 2011-2014, the PIVUS cohort showed decreases in circulating levels of some PFASs phased out of production with the exception of PFHxS and C>8 PFASs. Contrary to other studies, PFHxS concentrations showed the greatest overall increase, which is likely attributed to a local drinking water contamination incident.

  • 285.
    Stubleski, Jordan
    et al.
    MTM Research Centre, School of Science and Technology, Örebro University, 70182 Örebro, Sweden.
    Salihovic, Samira
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lind, P. Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Dunder, Linda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    McCleaf, Philip
    Uppsala Vatten och Avfall AB, Box 1105, 754 141 Uppsala.
    Eurén, Karin
    Uppsala Vatten och Avfall AB, Box 1105, 754 141 Uppsala.
    Ahrens, Lutz
    Swedish University of Agricultural Sciences (SLU), Department of Aquatic Sciences and Assessment, Gerda Nilssons väg 5, 756 51 Uppsala, Sweden.
    Svartengren, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    van Bavel, Bert
    MTM Research Centre, School of Science and Technology, Örebro University, 70182 Örebro, Sweden.; Norwegian Institute for Water Research, NIVA, 0349 Oslo, Norway.
    Kärrman, Anna
    MTM Research Centre, School of Science and Technology, Örebro University, 70182 Örebro, Sweden.
    The effect of drinking water contaminated with perfluoroalkyl substances on a 10-year longitudinal trend of plasma levels in an elderly Uppsala cohort2017Inngår i: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 159, s. 95-102, artikkel-id S0013-9351(17)30897-6Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: In 2012, drinking water contaminated with per- and polyfluoroalkyl substances (PFASs), foremost perfluorooctanesulfonic acid (PFOS) and perfluorohexanesulfonic acid (PFHxS) at levels over 20ng/L and 40ng/L, respectively, was confirmed in Uppsala, Sweden.

    OBJECTIVES: We assessed how a longitudinally sampled cohort's temporal trend in PFAS plasma concentration was influenced by their residential location and determined the plausible association or disparity between the PFASs detected in the drinking water and the trend in the study cohort.

    METHODS: The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort provided plasma samples three times from 2001 to 2014. Individuals maintaining the same zip code throughout the study (n = 399) were divided into a reference (no known PFAS exposure), low, intermediate and high exposure area depending on the proportion of contaminated drinking water received. Eight PFASs detected in the majority (75%) of the cohort's plasma samples were evaluated for significant changes in temporal PFAS concentrations using a random effects (mixed) model.

    RESULTS: PFHxS plasma concentrations continued to significantly increase in individuals living in areas receiving the largest percentage of contaminated drinking water (p < 0.0001), while PFOS showed an overall decrease. The temporal trend of other PFAS plasma concentrations did not show an association to the quality of drinking water received.

    CONCLUSIONS: The distribution of contaminated drinking water had a direct effect on the trend in PFHxS plasma levels among the different exposure groups, resulting in increased concentrations over time, especially in the intermediate and high exposure areas. PFOS and the remaining PFASs did not show the same relationship, suggesting other sources of exposure influenced these PFAS plasma trends.

  • 286. Surakka, Ida
    et al.
    Horikoshi, Momoko
    Magi, Reedik
    Sarin, Antti-Pekka
    Mahajan, Anubha
    Lagou, Vasiliki
    Marullo, Letizia
    Ferreira, Teresa
    Miraglio, Benjamin
    Timonen, Sanna
    Kettunen, Johannes
    Pirinen, Matti
    Karjalainen, Julia
    Thorleifsson, Gudmar
    Hägg, Sara
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Hottenga, Jouke-Jan
    Isaacs, Aaron
    Ladenvall, Claes
    Beekman, Marian
    Esko, Tonu
    Ried, Janina S.
    Nelson, Christopher P.
    Willenborg, Christina
    Gustafsson, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Westra, Harm-Jan
    Blades, Matthew
    de Craen, Anton J. M.
    de Geus, Eco J.
    Deelen, Joris
    Grallert, Harald
    Hamsten, Anders
    Havulinna, Aki S.
    Hengstenberg, Christian
    Houwing-Duistermaat, Jeanine J.
    Hypponen, Elina
    Karssen, Lennart C.
    Lehtimaki, Terho
    Lyssenko, Valeriya
    Magnusson, Patrik K. E.
    Mihailov, Evelin
    Muller-Nurasyid, Martina
    Mpindi, John-Patrick
    Pedersen, Nancy L.
    Penninx, Brenda W. J. H.
    Perola, Markus
    Pers, Tune H.
    Peters, Annette
    Rung, Johan
    Smit, Johannes H.
    Steinthorsdottir, Valgerdur
    Tobin, Martin D.
    Tsernikova, Natalia
    van Leeuwen, Elisabeth M.
    Viikari, Jorma S.
    Willems, Sara M.
    Willemsen, Gonneke
    Schunkert, Heribert
    Erdmann, Jeanette
    Samani, Nilesh J.
    Kaprio, Jaakko
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Gieger, Christian
    Metspalu, Andres
    Slagboom, P. Eline
    Groop, Leif
    van Duijn, Cornelia M.
    Eriksson, Johan G.
    Jula, Antti
    Salomaa, Veikko
    Boomsma, Dorret I.
    Power, Christine
    Raitakari, Olli T.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Jarvelin, Marjo-Riitta
    Thorsteinsdottir, Unnur
    Franke, Lude
    Ikonen, Elina
    Kallioniemi, Olli
    Pietiainen, Vilja
    Lindgren, Cecilia M.
    Stefansson, Kari
    Palotie, Aarno
    McCarthy, Mark I.
    Morris, Andrew P.
    Prokopenko, Inga
    Ripatti, Samuli
    The impact of low-frequency and rare variants on lipid levels2015Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 47, nr 6, s. 589-597Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Using a genome-wide screen of 9.6 million genetic variants achieved through 1000 Genomes Project imputation in 62,166 samples, we identify association to lipid traits in 93 loci, including 79 previously identified loci with new lead SNPs and 10 new loci, 15 loci with a low-frequency lead SNP and 10 loci with a missense lead SNP, and 2 loci with an accumulation of rare variants. In six loci, SNPs with established function in lipid genetics (CELSR2, GCKR, LIPC and APOE) or candidate missense mutations with predicted damaging function (CD300LG and TM6SF2) explained the locus associations. The low-frequency variants increased the proportion of variance explained, particularly for low-density lipoprotein cholesterol and total cholesterol. Altogether, our results highlight the impact of low-frequency variants in complex traits and show that imputation offers a cost-effective alternative to resequencing.

  • 287.
    Surendran, Praveen
    et al.
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England..
    Drenos, Fotios
    Univ Bristol, Sch Social & Community Med, Med Res Council Integrat Epidemiol Unit, Oakfield House, Bristol, Avon, England.;UCL, Inst Cardiovasc Sci, Ctr Cardiovasc Genet, London, England..
    Young, Robin
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England..
    Warren, Helen
    Queen Mary Univ London, William Harvey Res Inst, Clin Pharmacol, London, England.;Queen Mary Univ London, Natl Inst Hlth Res, Barts Cardiovasc Biomed Res Unit, London, England..
    Cook, James P.
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England.;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England..
    Manning, Alisa K.
    Harvard Med Sch, Dept Genet, Boston, MA USA.;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA..
    Grarup, Niels
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Sim, Xueling
    Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Biostat, Ann Arbor, MI USA.;Natl Univ Singapore, Natl Univ Hlth Syst, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Barnes, Daniel R.
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England..
    Witkowska, Kate
    Queen Mary Univ London, William Harvey Res Inst, Clin Pharmacol, London, England.;Queen Mary Univ London, Natl Inst Hlth Res, Barts Cardiovasc Biomed Res Unit, London, England..
    Staley, James R.
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England..
    Tragante, Vinicius
    Univ Med Ctr Utrecht, Dept Cardiol, Utrecht, Netherlands..
    Tukiainen, Taru
    Harvard Med Sch, Dept Genet, Boston, MA USA.;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA..
    Yaghootkar, Hanieh
    Univ Exeter, Inst Biomed & Clin Sci, Genet Complex Traits, Sch Med, Exeter, Devon, England..
    Masca, Nicholas
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.;Natl Inst Hlth, Res Leicester Biomed Res Unit Cardiovasc Dis, Leicester, Leics, England..
    Freitag, Daniel F.
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England..
    Ferreira, Teresa
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    Giannakopoulou, Olga
    Queen Mary Univ London, William Harvey Res Inst, Bads & London Sch Med & Dent, Ctr Heart, London, England..
    Tinker, Andrew
    Queen Mary Univ London, Natl Inst Hlth Res, Barts Cardiovasc Biomed Res Unit, London, England.;Queen Mary Univ London, William Harvey Res Inst, Bads & London Sch Med & Dent, Ctr Heart, London, England..
    Harakalova, Magdalena
    Univ Med Ctr Utrecht, Dept Cardiol, Utrecht, Netherlands..
    Mihailov, Evelin
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Liu, Chunyu
    NHLBI, Framingham, MA USA.;Boston Univ, Framingham Heart Study, Framingham, MA USA..
    Kraja, Aldi T.
    Washington Univ, Ctr Genome Sci & Syst Biol, Div Stat Genom, Sch Med, St Louis, MO USA.;Washington Univ, Dept Genet, Sch Med, St Louis, MO USA..
    Nielsen, Sune Fallgaard
    Copenhagen Univ Hosp, Dept Clin Biochem, Herlev Hosp, Herlev, Denmark..
    Rasheed, Asif
    Ctr Noncommunicable Dis, Karachi, Pakistan..
    Samue, Maria
    Ctr Noncommunicable Dis, Karachi, Pakistan..
    Zhao, Wei
    Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA..
    Bonnycastle, Lori L.
    NHGRI, Med Genom & Metab Genet Branch, US Natl Inst Hlth, Bethesda, MD 20892 USA..
    Jackson, Anne U.
    Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Biostat, Ann Arbor, MI USA..
    Narisu, Narisu
    NHGRI, Med Genom & Metab Genet Branch, US Natl Inst Hlth, Bethesda, MD 20892 USA..
    Swift, Amy J.
    NHGRI, Med Genom & Metab Genet Branch, US Natl Inst Hlth, Bethesda, MD 20892 USA..
    Southam, Lorraine
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Wellcome Trust Sanger Inst, Genome Campus, Hinxton, England..
    Marten, Jonathan
    Univ Edinburgh, Med Res Council Human Genet Unit, Med Res Council Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland..
    Huyghe, Jeroen R.
    Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Biostat, Ann Arbor, MI USA..
    Stancakova, Alena
    Univ Eastern Finland, Dept Med, Kuopio, Finland.;Kuopio Univ Hosp, Kuopio, Finland..
    Fava, Cristiano
    Lund Univ, Dept Clin Sci, Malmo, Sweden.;Univ Verona, Dept Med, Verona, Italy..
    Ohlsson, Therese
    Lund Univ, Dept Clin Sci, Malmo, Sweden..
    Matchan, Angela
    Wellcome Trust Sanger Inst, Genome Campus, Hinxton, England..
    Stirrups, Kathleen E.
    Queen Mary Univ London, William Harvey Res Inst, Bads & London Sch Med & Dent, Ctr Heart, London, England.;Univ Cambridge, Dept Haematol, Cambridge, England..
    Bork-Jensen, Jette
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Gjesing, Anette P.
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Kontto, Jukka
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland..
    Perola, Markus
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.;Univ Helsinki, Inst Mol Med FIMM, Helsinki, Finland..
    Shaw-Hawkins, Susan
    Queen Mary Univ London, William Harvey Res Inst, Clin Pharmacol, London, England..
    Havulinna, Aki S.
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland..
    Zhang, He
    Univ Michigan, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA..
    Donnelly, Louise A.
    Univ Dundee, Med Res Inst, Ninewells Hosp & Med Sch, Dundee, Scotland..
    Groves, Christopher J.
    Univ Oxford, Radcliffe Dept Med, Ctr Diabet, Endocrinol & Metab, Oxford, England..
    Rayner, N. William
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Wellcome Trust Sanger Inst, Genome Campus, Hinxton, England.;Univ Oxford, Radcliffe Dept Med, Ctr Diabet, Endocrinol & Metab, Oxford, England..
    Neville, Matt J.
    Univ Oxford, Radcliffe Dept Med, Ctr Diabet, Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trusts, Natl Inst Hlth, Res Oxford Biomed Res Ctr, Oxford, England..
    Robertson, Neil R.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Ctr Diabet, Endocrinol & Metab, Oxford, England..
    Yiorkas, Andrianos M.
    Imperial Coll London, Sect Invest Med, London, England.;Brunel Univ London, Dept Life Sci, London, England..
    Herzig, Karl-Heinz
    Univ Oulu, Inst Biomed, Bioctr Oulu, Oulu, Finland.;Poznan Univ Med Sci, Dept Gastroenterol & Metab, Poznan, Poland..
    Kajantie, Eero
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.;Univ Helsinki, Cent Hosp, Hosp Children & Adolescents, Helsinki, Finland.;Univ Helsinki, Helsinki, Finland.;Oulu Univ Hosp, Dept Obstet & Gynaecol, Oulu, Finland.;Univ Oulu, Oulu, Finland..
    Zhang, Weihua
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Ealing Gen Hosp, Dept Cardiol, Middlesex, Middx, England..
    Willems, Sara M.
    Univ Cambridge, Sch Clin Med, Med Res Council Epidemiol Unit, Inst Metab Sci, Cambridge Biomed Campus, Cambridge, England..
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Malerba, Giovanni
    Univ Verona, Dept Neurosci Biomed & Movement Sci, Sect Biol & Genet, Verona, Italy..
    Soranzo, Nicole
    Univ Cambridge, Dept Haematol, Cambridge, England.;Wellcome Trust Sanger Inst, Human Genet, Hinxton, England.;Univ Cambridge, NIHR Blbod & Transplant Res Unit Donor Hlth & Gen, Cambridge, England..
    Trabetti, Elisabetta
    Univ Verona, Dept Neurosci Biomed & Movement Sci, Sect Biol & Genet, Verona, Italy..
    Verweij, Niek
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA..
    Evangelou, Evangelos
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Univ Ioannina, Dept Hyg & Epidemiol, Sch Med, Ioannina, Greece..
    Moayyeri, Alireza
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;UCL, Farr Inst Hlth Informat Res, Inst Hlth Informat, London, England..
    Vergnaud, Anne-Claire
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England..
    Nelson, Christopher P.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.;Natl Inst Hlth, Res Leicester Biomed Res Unit Cardiovasc Dis, Leicester, Leics, England..
    Poveda, Alaitz
    Lund Univ, Genet & Mol Epidemiol Unit, Dept Clin Sci, Malmo, Sweden.;Univ Basque Country UPV EHU, Fac Sci & Technol, Dept Genet Phys Anthropol & Anim Physiol, Bilbao, Spain..
    Varga, Tibor V.
    Lund Univ, Genet & Mol Epidemiol Unit, Dept Clin Sci, Malmo, Sweden..
    Caslake, Muriel
    Univ Glasgow, Cardiovasc & Med Sci, Glasgow, Lanark, Scotland..
    de Craen, Anton J. M.
    Leiden Univ, Dept Gerontol & Geriatr, Med Ctr, Leiden, Netherlands..
    Trompet, Stella
    Leiden Univ, Dept Gerontol & Geriatr, Med Ctr, Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands..
    Luan, Jian'an
    Univ Cambridge, Sch Clin Med, Med Res Council Epidemiol Unit, Inst Metab Sci, Cambridge Biomed Campus, Cambridge, England..
    Scott, Robert A.
    Univ Cambridge, Sch Clin Med, Med Res Council Epidemiol Unit, Inst Metab Sci, Cambridge Biomed Campus, Cambridge, England..
    Harris, Sarah E.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Med Res Council Inst Genet & Mol Med, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland..
    Liewald, David C. M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland..
    Marioni, Riccardo
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Med Res Council Inst Genet & Mol Med, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland.;Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia..
    Menni, Cristina
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Farmaki, Aliki-Eleni
    Harokopio Univ, Sch Hlth Sci & Educ, Dept Nutr & Dietet, Athens, Greece..
    Hallmans, Goran
    Umea Univ, Dept Biobank Res, Umea, Sweden..
    Renstrom, Frida
    Lund Univ, Genet & Mol Epidemiol Unit, Dept Clin Sci, Malmo, Sweden.;Umea Univ, Dept Biobank Res, Umea, Sweden..
    Huffman, Jennifer E.
    NHLBI, Framingham, MA USA.;Boston Univ, Framingham Heart Study, Framingham, MA USA.;Univ Edinburgh, Med Res Council Human Genet Unit, Med Res Council Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland..
    Hassinen, Maija
    Kuopio Res Inst Exercise Med, Kuopio, Finland..
    Burgess, Stephen
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England..
    Vasan, Ramachandran S.
    NHLBI, Framingham, MA USA.;Boston Univ, Framingham Heart Study, Framingham, MA USA.;Boston Univ, Dept Med, Sect Cardiol, Sch Med, Boston, MA USA.;Boston Univ, Sch Publ Hlth, Boston, MA USA.;Boston Univ, Dept Med, Sect Prevent Med, Sch Med, Boston, MA USA.;Boston Univ, Dept Med, Sect Epidemiol, Sch Med, Boston, MA USA.;Boston Univ, Sch Publ Hlth, Boston, MA USA..
    Felix, Janine F.
    Erasmus MC, Univ Med Ctr Rotterdam, Dept Epidemiol, Rotterdam, Netherlands..
    Uria-Nickelsen, Maria
    Pfizer Worldwide Res & Dev, Dev Management & Planning, Cambridge, MA USA..
    Malarstign, Anders
    Pfizer Worldwide Res & Dev, Stockholm, Sweden..
    Reilly, Dermot F.
    Merck Res Labs, Genet & Pharmacogen, Boston, MA USA..
    Hoek, Maarten
    Merck Res Labs, Cardiometab Dis, Kenilworth, NJ USA..
    Vogt, Thomas F.
    Merck Res Labs, Cardiometab Dis, Kenilworth, NJ USA.;CHDI Management CHDI Fdn, Princeton, NJ USA..
    Lin, Honghuang
    NHLBI, Framingham, MA USA.;Boston Univ, Framingham Heart Study, Framingham, MA USA.;Boston Univ, Sch Med, Dept Med, Sect Computat Biomed, Boston, MA 02215 USA..
    Lieb, Wolfgang
    Univ Kiel, Inst Epidemiol & Biobank Popgen, Kiel, Germany..
    Traylor, Matthew
    Univ Cambridge, Neurol Unit, Cambridge Biomed Campus, Cambridge, England..
    Markus, Hugh S.
    Univ Cambridge, Neurol Unit, Cambridge Biomed Campus, Cambridge, England..
    Highland, Heather M.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA..
    Justice, Anne E.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA..
    Marouli, Eirini
    Queen Mary Univ London, William Harvey Res Inst, Bads & London Sch Med & Dent, Ctr Heart, London, England..
    Lindstrom, Jaana
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland..
    Uusitupa, Matti
    Univ Eastern Finland, Dept Publ Hlth & Clin Nutr, Kuopio, Finland.;Kuopio Univ Hosp, Res Unit, Kuopio, Finland..
    Komulainen, Pirjo
    Kuopio Res Inst Exercise Med, Kuopio, Finland..
    Lakka, Timo A.
    Kuopio Res Inst Exercise Med, Kuopio, Finland.;Univ Eastern Finland, Inst Biomed Physiol, Kuopio Campus, Kuopio, Finland.;Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, Kuopio, Finland..
    Rauramaa, Rainer
    Kuopio Res Inst Exercise Med, Kuopio, Finland.;Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, Kuopio, Finland..
    Polasek, Ozren
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland.;Univ Split, Fac Med, Split, Croatia..
    Rudan, Igor
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland..
    Rolandsson, Olov
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Franks, Paul W.
    Lund Univ, Genet & Mol Epidemiol Unit, Dept Clin Sci, Malmo, Sweden.;Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.;Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA..
    Dedoussis, George
    Harokopio Univ, Sch Hlth Sci & Educ, Dept Nutr & Dietet, Athens, Greece..
    Spector, Timothy D.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Jousilahti, Pekka
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland..
    Mannisto, Satu
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland..
    Deary, Ian J.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland..
    Starr, John M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh, Midlothian, Scotland..
    Langenberg, Claudia
    Univ Cambridge, Sch Clin Med, Med Res Council Epidemiol Unit, Inst Metab Sci, Cambridge Biomed Campus, Cambridge, England..
    Wareham, Nick J.
    Univ Cambridge, Sch Clin Med, Med Res Council Epidemiol Unit, Inst Metab Sci, Cambridge Biomed Campus, Cambridge, England..
    Brown, Morris J.
    Queen Mary Univ London, William Harvey Res Inst, Clin Pharmacol, London, England..
    Dominiczak, Anna F.
    Univ Glasgow, Coll Med Vet & Life Sci, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland..
    Connell, John M.
    Univ Dundee, Med Res Inst, Ninewells Hosp & Med Sch, Dundee, Scotland..
    Jukema, J. Wouter
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands.;Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands..
    Sattar, Naveed
    Univ Glasgow, Coll Med Vet & Life Sci, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland..
    Ford, Ian
    Univ Glasgow, Cardiovasc & Med Sci, Glasgow, Lanark, Scotland..
    Packard, Chris J.
    Univ Glasgow, Cardiovasc & Med Sci, Glasgow, Lanark, Scotland..
    Esko, Tonu
    Harvard Med Sch, Dept Genet, Boston, MA USA.;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Boston Childrens Hosp, Div Endocrinol, Boston, MA USA..
    Magi, Reedik
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Inst Mol & Cell Biol, Tartu, Estonia..
    de Boer, Rudolf A.
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands..
    van der Meer, Peter
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands..
    van der Harst, Pim
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.;Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands.;ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands..
    Gambaro, Giovanni
    Catholic Univ, Columbus Gemelli Univ Hosp, Dept Internal Med & Med Speciales, Div Nephrol, Rome, Italy..
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    de Bakker, Paul I. W.
    Univ Med Ctr Utrecht, Ctr Mol Med, Dept Med Genet, Utrecht, Netherlands.;Univ Med Ctr Utrecht, Dept Epidemiol, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands..
    Numans, Mattijs E.
    Univ Med Ctr Utrecht, Dept Epidemiol, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.;Leiden Univ, Dept Publ Hlth & Primary Care, Med Ctr, Leiden, Netherlands.;Imperial Coll Healthcare NHS Trust, London, England..
    Brandslund, Ivan
    Lillebaelt Hosp, Dept Clin Biochem, Vejle, Denmark.;Univ Southern Denmark, Inst Reg Hlth Res, Odense, Denmark..
    Christensen, Cramer
    Lillebaelt Hosp, Dept Med, Vejle, Denmark..
    Petersen, Eva R. B.
    Lillebaelt Hosp, Dept Clin Immunol & Biochem, Vejle, Denmark..
    Korpi-Hyovalti, Eeva
    South Ostrobothnia Cent Hosp, Dept Internal Med, Seinajoki, Finland..
    Oksa, Heikki
    Tampere Univ Hosp, Dept Internal Med, Tampere, Finland..
    Chambers, John C.
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Ealing Gen Hosp, Dept Cardiol, Middlesex, Middx, England.;Imperial Coll Healthcare NHS Trust, London, England..
    Kooner, Jaspal S.
    Ealing Gen Hosp, Dept Cardiol, Middlesex, Middx, England.;Imperial Coll London, Natl Heart & Lung Inst, London, England..
    Blakemore, Alexandra I. F.
    Imperial Coll London, Sect Invest Med, London, England.;Brunel Univ London, Dept Life Sci, London, England..
    Franks, Steve
    Imperial Coll London, Inst Reprod & Dev Biol, London, England..
    Jarvelin, Marjo-Riitta
    Imperial Coll London, Dept Epidemiol & Biostat, Med Res Council Publ Hlth England Ctr Environm &, Sch Publ Hlth,Fac Med, St Marys Campus, London, England.;Univ Oulu, Ctr Life Course Hlth Res, Fac Med, Oulu, Finland.;Univ Oulu, Bioctr Oulu, Oulu, Finland.;Oulu Univ Hosp, Unit Primary Care, Oulu, Finland..
    Husemoen, Lise L.
    Capital Reg Denmark, Res Ctr Prevent & Hlth, Copenhagen, Denmark..
    Linneberg, Allan
    Capital Reg Denmark, Res Ctr Prevent & Hlth, Copenhagen, Denmark.;Glostrup Univ Hosp, Dept Clin Expt Res, Glostrup, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark..
    Skaaby, Tea
    Capital Reg Denmark, Res Ctr Prevent & Hlth, Copenhagen, Denmark..
    Thuesen, Betina
    Capital Reg Denmark, Res Ctr Prevent & Hlth, Copenhagen, Denmark..
    Karpe, Fredrik
    Univ Oxford, Radcliffe Dept Med, Ctr Diabet, Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trusts, Natl Inst Hlth, Res Oxford Biomed Res Ctr, Oxford, England..
    Tuomilehto, Jaakko
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.;Dasman Diabet Inst, Kuwait, Kuwait.;Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria.;King Abdulaziz Univ, Diabet Res Grp, Jeddah, Saudi Arabia..
    Doney, Alex S. F.
    Univ Dundee, Med Res Inst, Ninewells Hosp & Med Sch, Dundee, Scotland..
    Morris, Andrew D.
    Univ Edinburgh, Sch Med, Sch Mol Genet & Populat Hlth Sci, Teviot Pl, Edinburgh, Midlothian, Scotland..
    Palmer, Colin N. A.
    Univ Dundee, Med Res Inst, Ninewells Hosp & Med Sch, Dundee, Scotland..
    Holmen, Oddgeir Lingaas
    Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, Levanger, Norway.;Univ Trondheim Hosp, St Olav Hosp, Trondheim, Norway..
    Hveem, Kristian
    Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, Levanger, Norway.;Nord Trondelag Hlth Trust, Levanger Hosp, Dept Med, Levanger, Norway..
    Willer, Cristen J.
    Univ Michigan, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA..
    Tuomi, Tiinamaija
    Folkhalsan Res Ctr, Helsinki, Finland.;Univ Helsinki, Dept Endocrinol, Cent Hosp, Helsinki, Finland.;Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland..
    Groop, Leif
    Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland.;Lund Univ, Dept Clin Sci Diabet & Endocrinol, Ctr Diabet, Malmo, Sweden..
    Karajamaki, AnneMari
    Vaasa Cent Hosp, Dept Primary Hlth Care, Vaasa, Finland.;Vaasa Hlth Care Ctr, Ctr Diabet, Vaasa, Finland..
    Palotie, Aarno
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA.;Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland.;Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA..
    Ripatti, Samuli
    Wellcome Trust Sanger Inst, Genome Campus, Hinxton, England.;Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland.;Univ Helsinki, Dept Publ Hlth, Helsinki, Finland..
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland..
    Alam, Dewan S.
    ICDDR, Dhaka, Bangladesh..
    Majmnder, Abdulla Al Shafi
    Natl Inst Cardiovasc Dis, Dhaka, Bangladesh..
    Di Angelantonio, Emanuele
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England.;Univ Cambridge, NIHR Blbod & Transplant Res Unit Donor Hlth & Gen, Cambridge, England..
    Chowdhury, Rajiv
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England..
    McCarthy, Mark I.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Ctr Diabet, Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trusts, Natl Inst Hlth, Res Oxford Biomed Res Ctr, Oxford, England..
    Poulter, Neil
    Imperial Coll London, Sch Publ Hlth, London, England..
    Stanton, Alice V.
    Royal Coll Surgeons Ireland, Mol & Cellular Therapeut, Dublin, Ireland..
    Sever, Peter
    Imperial Coll London, Natl Heart & Lung Inst, London, England..
    Amouyel, Philippe
    Univ Lille, UMR 1167, Risk Factors & Mol Determinants Aging Related Dis, Lille, France.;INSERM, Lille, France.;CHU Lille, Publ Hlth, Lille, France.;Inst Pasteur, Lille, France..
    Arveiler, Dominique
    Univ Strasbourg, Dept Epidemiol & Publ Hlth, EA 3430, Strasbourg, France..
    Blankenberg, Stefan
    Univ Heart Ctr Hamburg, Dept Gen & Intervent Cardiol, Hamburg, Germany.;Univ Med Ctr Hamburg Eppendorf, Hamburg, Germany..
    Ferrieres, Jean
    Toulouse Univ, Dept Epidemiol, UMR 1027, INSERM,CHU Toulouse, Toulouse, France..
    Kee, Frank
    Queens Univ, UKCRC Ctr Excellence Publ Hlth, Belfast, Antrim, North Ireland..
    Kuulasmaa, Kari
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland..
    Muller-Nurasyid, Martina
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Genet Epidemiol, Neuherberg, Germany.;Univ Munich, Dept Med 1, Univ Hosp Grosshadern, Munich, Germany.;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany..
    Veronesi, Giovanni
    Univ Insubria, Dept Clin & Expt Med, Res Ctr Epidemiol & Prevent Med, Varese, Italy..
    Virtamo, Jarmo
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland..
    Deloukas, Panos
    Queen Mary Univ London, William Harvey Res Inst, Bads & London Sch Med & Dent, Ctr Heart, London, England.;King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah, Saudi Arabia..
    Elliott, Paul
    Imperial Coll London, Dept Epidemiol & Biostat, Med Res Council Publ Hlth England Ctr Environm &, Sch Publ Hlth,Fac Med, St Marys Campus, London, England..
    Zeggini, Eleftheria
    Wellcome Trust Sanger Inst, Genome Campus, Hinxton, England..
    Kathiresan, Sekar
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Boston, MA 02114 USA.;Harvard Med Sch, Dept Med, Boston, MA USA..
    Melander, Olle
    Lund Univ, Dept Clin Sci, Malmo, Sweden..
    Kuusisto, Johanna
    Univ Eastern Finland, Dept Med, Kuopio, Finland.;Kuopio Univ Hosp, Kuopio, Finland..
    Laakso, Markku
    Univ Eastern Finland, Dept Med, Kuopio, Finland.;Kuopio Univ Hosp, Kuopio, Finland..
    Padmanabhan, Sandosh
    Univ Glasgow, Coll Med Vet & Life Sci, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland..
    Porteous, David J.
    Univ Edinburgh, Med Res Council Inst Genet & Mol Med, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland..
    Hayward, Caroline
    Univ Edinburgh, Med Res Council Human Genet Unit, Med Res Council Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland..
    Scotland, Generation
    Collaborat Univ Med Sch & NHS, Aberdeen, Scotland.;Collaborat Univ Med Sch & NHS, Dundee, Scotland.;Collaborat Univ Med Sch & NHS, Edinburgh, Midlothian, Scotland.;Collaborat Univ Med Sch & NHS, Glasgow, Lanark, Scotland..
    Collins, Francis S.
    NHGRI, Med Genom & Metab Genet Branch, US Natl Inst Hlth, Bethesda, MD 20892 USA..
    Mohlke, Karen L.
    Univ N Carolina, Dept Genet, Chapel Hill, NC USA..
    Hansen, Torben
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Pedersen, Oluf
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Boehnke, Michael
    Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Biostat, Ann Arbor, MI USA..
    Stringham, Heather M.
    Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Biostat, Ann Arbor, MI USA..
    Frossard, Philippe
    Ctr Noncommunicable Dis, Karachi, Pakistan..
    Newton-Cheh, Christopher
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Boston, MA 02114 USA..
    Tobin, Martin D.
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
    Nordestgaard, Borge Gronne
    Copenhagen Univ Hosp, Dept Clin Biochem, Herlev Hosp, Herlev, Denmark..
    Caulfield, Mark J.
    Queen Mary Univ London, William Harvey Res Inst, Clin Pharmacol, London, England.;Queen Mary Univ London, Natl Inst Hlth Res, Barts Cardiovasc Biomed Res Unit, London, England..
    Mahajan, Anubha
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    Morris, Andrew P.
    Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.;Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    Tomaszewski, Maciej
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.;Natl Inst Hlth, Res Leicester Biomed Res Unit Cardiovasc Dis, Leicester, Leics, England.;Univ Manchester, Div Cardiovasc Sci, Manchester, Lancs, England..
    Samani, Nilesh J.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.;Natl Inst Hlth, Res Leicester Biomed Res Unit Cardiovasc Dis, Leicester, Leics, England..
    Saleheen, Danish
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England.;Ctr Noncommunicable Dis, Karachi, Pakistan.;Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA..
    Asselbergs, Folkert W.
    Univ Med Ctr Utrecht, Dept Cardiol, Utrecht, Netherlands.;ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands.;UCL, Inst Cardiovasc Sci, Fac Populat Hlth Sci, London, England..
    Lindgren, Cecilia M.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Big Data Inst, Li Ka Shing Ctr Hlth Informat & Discovery, Oxford, England..
    Danesh, John
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England.;Univ Cambridge, NIHR Blbod & Transplant Res Unit Donor Hlth & Gen, Cambridge, England.;Wellcome Trust Sanger Inst, Hinxton, England..
    Wain, Louise V.
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
    Butterworth, Adam S.
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England.;Univ Cambridge, NIHR Blbod & Transplant Res Unit Donor Hlth & Gen, Cambridge, England..
    Howson, Joanna M. M.
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England..
    Munroe, Patricia B.
    Queen Mary Univ London, William Harvey Res Inst, Clin Pharmacol, London, England.;Queen Mary Univ London, Natl Inst Hlth Res, Barts Cardiovasc Biomed Res Unit, London, England.;Wellcome Trust Sanger Inst, Hinxton, England..
    Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension2016Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 48, nr 10, s. 1151-1161Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low frequency and common genetic variants in up to 192,763 individuals and used similar to 155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.

  • 288. Swaminathan, Bhairavi
    et al.
    Thorleifsson, Guomar
    Joud, Magnus
    Ali, Mina
    Johnsson, Ellinor
    Ajore, Ram
    Sulem, Patrick
    Halvarsson, Britt-Marie
    Eyjolfsson, Guomundur
    Haraldsdottir, Vilhelmina
    Hultman, Christina
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Kristinsson, Sigurour Y.
    Kahler, Anna K.
    Lenhoff, Stig
    Masson, Gisli
    Mellqvist, Ulf-Henrik
    Mansson, Robert
    Nelander, Sven
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Neuroonkologi.
    Olafsson, Isleifur
    Siguroardottir, Olof
    Steingrimsdottir, Hlif
    Vangsted, Annette
    Vogel, Ulla
    Waage, Anders
    Nahi, Hareth
    Gudbjartsson, Daniel F.
    Rafnar, Thorunn
    Turesson, Ingemar
    Gullberg, Urban
    Stefansson, Kari
    Hansson, Markus
    Thorsteinsdottir, Unnur
    Nilsson, Bjorn
    Variants in ELL2 influencing immunoglobulin levels associate with multiple myeloma2015Inngår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 6, artikkel-id 7213Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Multiple myeloma (MM) is characterized by an uninhibited, clonal growth of plasma cells. While first-degree relatives of patients with MM show an increased risk of MM, the genetic basis of inherited MM susceptibility is incompletely understood. Here we report a genome-wide association study in the Nordic region identifying a novel MM risk locus at ELL2 (rs56219066T; odds ratio (OR) = 1.25; P = 9.6 x 10(-10)). This gene encodes a stoichiometrically limiting component of the super-elongation complex that drives secretory-specific immunoglobulin mRNA production and transcriptional regulation in plasma cells. We find that the MM risk allele harbours a Thr298Ala missense variant in an ELL2 domain required for transcription elongation. Consistent with a hypomorphic effect, we find that the MM risk allele also associates with reduced levels of immunoglobulin A (IgA) and G (IgG) in healthy subjects (P = 8.6 x 10(-9) and P = 6.4 x 10(-3), respectively) and, potentially, with an increased risk of bacterial meningitis (OR = 1.30; P = 0.0024).

  • 289. Tang, Wenbo
    et al.
    Kowgier, Matthew
    Loth, Daan W.
    Artigas, Maria Soler
    Joubert, Bonnie R.
    Hodge, Emily
    Gharib, Sina A.
    Smith, Albert V.
    Ruczinski, Ingo
    Gudnason, Vilmundur
    Mathias, Rasika A.
    Harris, Tamara B.
    Hansel, Nadia N.
    Launer, Lenore J.
    Barnes, Kathleen C.
    Hansen, Joyanna G.
    Albrecht, Eva
    Aldrich, Melinda C.
    Allerhand, Michael
    Barr, R. Graham
    Brusselle, Guy G.
    Couper, David J.
    Curjuric, Ivan
    Davies, Gail
    Deary, Ian J.
    Dupuis, Josee
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Foy, Millennia
    Franceschini, Nora
    Gao, Wei
    Glaeser, Sven
    Gu, Xiangjun
    Hancock, Dana B.
    Heinrich, Joachim
    Hofman, Albert
    Imboden, Medea
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    James, Alan
    Karrasch, Stefan
    Koch, Beate
    Kritchevsky, Stephen B.
    Kumar, Ashish
    Lahousse, Lies
    Li, Guo
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Lindgren, Cecilia
    Liu, Yongmei
    Lohman, Kurt
    Lumley, Thomas
    McArdle, Wendy L.
    Meibohm, Bernd
    Morris, Andrew P.
    Morrison, Alanna C.
    Musk, Bill
    North, Kari E.
    Palmer, Lyle J.
    Probst-Hensch, Nicole M.
    Psaty, Bruce M.
    Rivadeneira, Fernando
    Rotter, Jerome I.
    Schulz, Holger
    Smith, Lewis J.
    Sood, Akshay
    Starr, John M.
    Strachan, David P.
    Teumer, Alexander
    Uitterlinden, Andre G.
    Voelzke, Henry
    Voorman, Arend
    Wain, Louise V.
    Wells, Martin T.
    Wilk, Jemma B.
    Williams, O. Dale
    Heckbert, Susan R.
    Stricker, Bruno H.
    London, Stephanie J.
    Fornage, Myriam
    Tobin, Martin D.
    O'Connor, George T.
    Hall, Ian P.
    Cassano, Patricia A.
    Large-Scale Genome-Wide Association Studies and Meta-Analyses of Longitudinal Change in Adult Lung Function2014Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 7, s. e100776-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function. Methods: We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis. Results: The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P = 5.71 x 10(-7)). In addition, meta-analysis using the five cohorts with >= 3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P = 2.18 x 10(-8)) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively. Conclusions: In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function.

  • 290.
    Teumer, Alexander
    et al.
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany.
    Li, Yong
    Univ Freiburg, Fac Med & Med Ctr, Dept Biometry Epidemiol & Med Bioinformat, Inst Genet Epidemiol, Freiburg, Germany.
    Ghasemi, Sahar
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany.
    Prins, Bram P.
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England.
    Wuttke, Matthias
    Univ Freiburg, Fac Med & Med Ctr, Dept Biometry Epidemiol & Med Bioinformat, Inst Genet Epidemiol, Freiburg, Germany;Univ Freiburg, Fac Med & Med Ctr, Dept Med, Renal Div, Freiburg, Germany.
    Hermle, Tobias
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA;Welch Ctr Prevent, Epidemiol & Clin Res, Baltimore, MD USA.
    Giri, Ayush
    Vanderbilt Univ, Med Ctr,Div Quantitat Sci, Dept Obstet & Gynecol,Vanderbilt Genet Inst, Inst Med & Publ Hlth,Vanderbilt Epidemiol Ctr, Nashville, TN 37232 USA;Vanderbilt Univ, Tennessee Valley Healthcare Syst 626, Biomed Lab Res & Dev, 221 Kirkland Hall, Nashville, TN 37235 USA.
    Sieber, Karsten B.
    GlaxoSmithKline, Target Sci Genet, Collegeville, PA USA.
    Qiu, Chengxiang
    Univ Penn, Dept Med, Dept Genet, Renal Elect & Hypertens,Div Perelman Sch Med, Philadelphia, PA 19104 USA.
    Kirsten, Holger
    Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany;Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany.
    Tin, Adrienne
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA;Welch Ctr Prevent, Epidemiol & Clin Res, Baltimore, MD USA.
    Chu, Audrey Y.
    Merck & Co Inc, Genet, Kenilworth, NJ USA.
    Bansal, Nisha
    Univ Washington, Div Nephrol, Seattle, WA 98195 USA;Univ Washington, Kidney Res Inst, Seattle, WA 98195 USA.
    Feitosa, Mary F.
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.
    Wang, Lihua
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.
    Chai, Jin-Fang
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore;Natl Univ Hlth Syst, Singapore, Singapore.
    Cocca, Massimiliano
    IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy.
    Fuchsberger, Christian
    Univ Lubeck, Inst Biomed, Eurac Res, Bolzano, Italy.
    Gorski, Mathias
    Univ Hosp Regensburg, Dept Nephrol, Regensburg, Germany;Univ Regensburg, Dept Genet Epidemiol, Regensburg, Germany.
    Hoppmann, Anselm
    Univ Freiburg, Fac Med & Med Ctr, Dept Biometry Epidemiol & Med Bioinformat, Inst Genet Epidemiol, Freiburg, Germany.
    Horn, Katrin
    Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany;Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany.
    Li, Man
    Univ Utah, Dept Med, Div Nephrol & Hypertens, Salt Lake City, UT 84112 USA.
    Marten, Jonathan
    Univ Edinburgh, Inst Genet & Mol Med, Med Res Council Human Genet Unit, Edinburgh, Midlothian, Scotland.
    Noce, Damia
    Univ Lubeck, Inst Biomed, Eurac Res, Bolzano, Italy.
    Nutile, Teresa
    CNR, Inst Genet & Biophys Adriano Buzzati Traveso, Naples, Italy.
    Sedaghat, Sanaz
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    Sveinbjornsson, Gardar
    Amgen Inc, deCODE Genet, Reykjavik, Iceland.
    Tayo, Bamidele O.
    Loyola Univ Chicago, Dept Publ Hlth Sci, Maywood, IL USA.
    Van der Most, Peter J.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.
    Xu, Yizhe
    Univ Utah, Dept Med, Div Nephrol & Hypertens, Salt Lake City, UT 84112 USA.
    Yu, Zhi
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA;Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA.
    Gerstner, Lea
    Univ Freiburg, Fac Med & Med Ctr, Dept Med, Renal Div, Freiburg, Germany.
    Arnlov, Johan
    Karolinska Inst, Div Family Med & Primary Care, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden;Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden.
    Bakker, Stephan J. L.
    Univ Groningen, Univ Med Ctr Groningen, Div Nephrol, Dept Internal Med, Groningen, Netherlands.
    Baptista, Daniela
    Geneva Univ Hosp, Cardiol, Geneva, Switzerland.
    Biggs, Mary L.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA;Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
    Boerwinkle, Eric
    Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Houston, TX 77030 USA.
    Brenner, Hermann
    German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany;Heidelberg Univ, Network Aging Res, Heidelberg, Germany.
    Burkhardt, Ralph
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany;Univ Leipzig, Inst Lab Med Clin Chem & Mol Diagnost, Leipzig, Germany;Univ Hosp Regensburg, Inst Clin Chem & Lab Med, Regensburg, Germany.
    Carroll, Robert J.
    Vanderbilt Univ, Med Ctr, Dept Biomed Informat, Nashville, TN USA.
    Chee, Miao-Li
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
    Chee, Miao-Ling
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
    Chen, Mengmeng
    Univ Freiburg, Fac Med & Med Ctr, Dept Med, Renal Div, Freiburg, Germany.
    Cheng, Ching-Yu
    Natl Univ Hlth Syst, Singapore, Singapore;Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore;Duke NUS Med Sch, Ophthalmol & Visual Sci Acad Clin Program Eye ACP, Singapore, Singapore;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.
    Cook, James P.
    Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.
    Coresh, Josef
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
    Corre, Tanguy
    Univ Lausanne, Ctr Primary Care & Publ Hlth Unisante, Lausanne, Switzerland;Univ Lausanne, Dept Computat Biol, Lausanne, Switzerland;Swiss Inst Bioinformat, Lausanne, Switzerland.
    Danesh, John
    Univ Cambridge, Sch Clin Med, Dept Publ Hlth & Primary Care, Cambridge, England.
    de Borst, Martin H.
    Univ Groningen, Univ Med Ctr Groningen, Div Nephrol, Dept Internal Med, Groningen, Netherlands.
    De Grandi, Alessandro
    Univ Lubeck, Inst Biomed, Eurac Res, Bolzano, Italy.
    de Mutsert, Renee
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands.
    de Vries, Aiko P. J.
    Leiden Univ, Med Ctr, Dept Internal Med, Sect Nephrol, Leiden, Netherlands.
    Degenhardt, Frauke
    Christian Albrechts Univ Kiel, Inst Clin Mol Biol, Kiel, Germany.
    Dittrich, Katalin
    Univ Leipzig, Hosp Children & Adolescents, Dept Women & Child Hlth, Leipzig, Germany;Univ Leipzig, Ctr Pediat Res, Leipzig, Germany.
    Divers, Jasmin
    Wake Forest Sch Med, Dept Biostat & Data Sci, Winston Salem, NC USA.
    Eckardt, Kai-Uwe
    Charite, Intens Care Med, Berlin, Germany;Friedrich Alexander Univ Erlangen Nurnberg FAU, Dept Nephrol & Hypertens, Erlangen, Germany.
    Ehret, Georg
    Geneva Univ Hosp, Cardiol, Geneva, Switzerland.
    Endlich, Karlhans
    DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany;Univ Med Greifswald, Dept Anat & Cell Biol, Greifswald, Germany.
    Felix, Janine F.
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus MC, Generat R Study Grp, Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus MC, Dept Pediat, Rotterdam, Netherlands.
    Franco, Oscar H.
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands;Univ Bern, ISPM, Bern, Switzerland.
    Franke, Andre
    Christian Albrechts Univ Kiel, Inst Clin Mol Biol, Kiel, Germany.
    Freedman, Barry I.
    Wake Forest Sch Med, Internal Med Sect Nephrol, Winston Salem, NC USA.
    Freitag-Wolf, Sandra
    Univ Kiel, Univ Hosp Schleswig Holstein, Inst Med Informat & Stat, Kiel, Germany.
    Gansevoort, Ron T.
    Univ Groningen, Univ Med Ctr Groningen, Div Nephrol, Dept Internal Med, Groningen, Netherlands.
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Gogele, Martin
    Univ Lubeck, Inst Biomed, Eurac Res, Bolzano, Italy.
    Grundner-Culemann, Franziska
    Univ Freiburg, Fac Med & Med Ctr, Dept Biometry Epidemiol & Med Bioinformat, Inst Genet Epidemiol, Freiburg, Germany.
    Gudbjartsson, Daniel F.
    Amgen Inc, deCODE Genet, Reykjavik, Iceland.
    Gudnason, Vilmundur
    Iceland Heart Assoc, Kopavogur, Iceland;Univ Iceland, Sch Hlth Sci, Fac Med, Reykjavik, Iceland.
    Hamet, Pavel
    CHUM, Montreal Univ Hosp Res Ctr, Montreal, PQ, Canada;Medpharmgene, Montreal, PQ, Canada.
    Harris, Tamara B.
    NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
    Hicks, Andrew A.
    Univ Lubeck, Inst Biomed, Eurac Res, Bolzano, Italy.
    Holm, Hilma
    Amgen Inc, deCODE Genet, Reykjavik, Iceland.
    Foo, Valencia Hui Xian
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
    Hwang, Shih-Jen
    NHLBIs Framingham Heart Study, Framingham, MA USA;NHLBI, Ctr Populat Studies, Framingham, MA USA.
    Ikram, M. Arfan
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    Ingelsson, Erik
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA;Stanford Univ, Stanford Diabet Res Ctr, Stanford, CA 94305 USA.
    Jaddoe, Vincent W. V.
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus MC, Generat R Study Grp, Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus MC, Dept Pediat, Rotterdam, Netherlands.
    Jakobsdottir, Johanna
    Iceland Heart Assoc, Holtasmari 1, IS-201 Kopavogur, Iceland;Univ Iceland, Ctr Publ Hlth Sci, Sturlugata 8, IS-101 Reykjavik, Iceland.
    Josyula, Navya Shilpa
    Geisinger Res Biomed & Translat Informat Inst, Rockville, MD USA.
    Jung, Bettina
    Univ Hosp Regensburg, Dept Nephrol, Regensburg, Germany.
    Kahonen, Mika
    Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland;Tampere Univ, Fac Med & Hlth Technol, Finnish Cardiovasc Res Ctr Tampere, Dept Clin Physiol, Tampere, Finland.
    Khor, Chiea-Chuen
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore;Agcy Sci Technol & Res, Genome Inst Singapore, Singapore, Singapore.
    Kiess, Wieland
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany;Univ Leipzig, Hosp Children & Adolescents, Dept Women & Child Hlth, Leipzig, Germany;Univ Leipzig, Ctr Pediat Res, Leipzig, Germany.
    Koenig, Wolfgang
    Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany;Univ Ulm, Inst Epidemiol & Biostat, Ulm, Germany.
    Koerner, Antje
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany;Univ Leipzig, Hosp Children & Adolescents, Dept Women & Child Hlth, Leipzig, Germany;Univ Leipzig, Ctr Pediat Res, Leipzig, Germany.
    Kovacs, Peter
    Univ Leipzig, Integrated Res & Treatment Ctr Adipos Dis, Leipzig, Germany.
    Kramer, Holly
    Loyola Univ Chicago, Dept Publ Hlth Sci, Maywood, IL USA;Loyola Univ Chicago, Div Nephrol & Hypertens, Chicago, IL USA.
    Kraemer, Bernhard K.
    Heidelberg Univ, Med Fac Mannheim, Dept Med Nephrol 5, Hypertensiol,Rheumatol,Endocrinol,Diabetol, Mannheim, Germany.
    Kronenberg, Florian
    Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, Innsbruck, Austria.
    Lange, Leslie A.
    Univ Colorado Denver, Sch Med, Div Biomed Informat & Personalized Med, Anschutz Med Campus, Aurora, CO USA.
    Langefeld, Carl D.
    Wake Forest Sch Med, Dept Biostat & Data Sci, Winston Salem, NC USA.
    Lee, Jeannette Jen-Mai
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore;Natl Univ Hlth Syst, Singapore, Singapore.
    Lehtimaki, Terho
    Fimlab Labs, Dept Clin Chem, Tampere, Finland;Tampere Univ, Fac Med & Hlth Technol, Finnish Cardiovasc Res Ctr Tampere, Dept Clin Chem, Tampere, Finland.
    Lieb, Wolfgang
    Univ Kiel, Inst Epidemiol, Kiel, Germany;Univ Kiel, Biobank Popgen, Kiel, Germany.
    Lim, Su-Chi
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore;Natl Univ Hlth Syst, Singapore, Singapore;Khoo Teck Puat Hosp, Diabetes Ctr, Singapore, Singapore.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Lindgren, Cecilia M.
    Univ Oxford, Nuffield Dept Med, Oxford, England;Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
    Liu, Jianjun
    Natl Univ Hlth Syst, Singapore, Singapore;Agcy Sci Technol & Res, Genome Inst Singapore, Singapore, Singapore;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore, Singapore.
    Loeffler, Markus
    Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany;Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany.
    Lyytikainen, Leo-Pekka
    Fimlab Labs, Dept Clin Chem, Tampere, Finland;Tampere Univ, Fac Med & Hlth Technol, Finnish Cardiovasc Res Ctr Tampere, Dept Clin Chem, Tampere, Finland.
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
    Maranville, Joseph C.
    Merck & Co Inc, MRL, Kenilworth, NJ USA;Celgene Inc, Cambridge, MA USA.
    Mascalzoni, Deborah
    Univ Lubeck, Inst Biomed, Eurac Res, Bolzano, Italy.
    McMullen, Barbara
    Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA.
    Meisinger, Christa
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Independent Res Grp Clin Epidemiol, Neuherberg, Germany;Ludwig Maximilians Univ Munchen, UNIKA T Augsburg, Chair Epidemiol, Augsburg, Germany.
    Meitinger, Thomas
    DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany;Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany;Tech Univ Munich, Inst Human Genet, Munich, Germany.
    Miliku, Kozeta
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus MC, Generat R Study Grp, Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus MC, Dept Pediat, Rotterdam, Netherlands.
    Mook-Kanamori, Dennis O.
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands;Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, Leiden, Netherlands.
    Mueller-Nurasyid, Martina
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany;LMU, Fac Med, IBE, Chair Genet Epidemiol, Munich, Germany;Hosp Ludwig Maximilians Univ LMU Munich, Dept Internal Med Cardiol 1, Munich, Germany.
    Mychaleckyj, Josyf C.
    Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
    Nauck, Matthias
    DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany;Univ Med Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany.
    Nikus, Kjell
    Tampere Univ Hosp, Heart Ctr, Dept Cardiol, Tampere, Finland;Tampere Univ, Fac Med & Hlth Technol, Finnish Cardiovasc Res Ctr Tampere, Dept Cardiol, Tampere, Finland.
    Ning, Boting
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
    Noordam, Raymond
    Leiden Univ, Med Ctr, Dept Internal Med, Sect Gerontol & Geriatr, Leiden, Netherlands.
    Connell, Jeffrey O'
    Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
    Olafsson, Isleifur
    Landspitali Univ Hosp, Dept Clin Biochem, Reykjavik, Iceland.
    Palmer, Nicholette D.
    Wake Forest Sch Med, Biochem, Winston Salem, NC USA.
    Peters, Annette
    DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany;German Ctr Diabet Res DZD, Neuherberg, Germany.
    Podgornaia, Anna I.
    Merck & Co Inc, Genet, Kenilworth, NJ USA.
    Ponte, Belen
    Geneva Univ Hosp, Serv Nephrol, Geneva, Switzerland.
    Poulain, Tanja
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany.
    Pramstaller, Peter P.
    Univ Lubeck, Inst Biomed, Eurac Res, Bolzano, Italy.
    Rabelink, Ton J.
    Leiden Univ, Med Ctr, Dept Internal Med, Sect Nephrol, Leiden, Netherlands;Leiden Univ, Med Ctr, Einthoven Lab Expt Vasc Res, Leiden, Netherlands.
    Raffield, Laura M.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA.
    Reilly, Dermot F.
    Merck & Co Inc, Genet, Kenilworth, NJ USA.
    Rettig, Rainer
    Univ Med Greifswald, Inst Physiol, Karlsburg, Germany.
    Rheinberger, Myriam
    Univ Hosp Regensburg, Dept Nephrol, Regensburg, Germany.
    Rice, Kenneth M.
    Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
    Rivadeneira, Fernando
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
    Runz, Heiko
    Merck & Co Inc, MRL, Kenilworth, NJ USA;Biogen Inc, 14 Cambridge Ctr, Cambridge, MA 02142 USA.
    Ryan, Kathleen A.
    Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
    Sabanayagam, Charumathi
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore;Duke NUS Med Sch, Ophthalmol & Visual Sci Acad Clin Program Eye ACP, Singapore, Singapore.
    Saum, Kai-Uwe
    German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
    Schoettker, Ben
    German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany;Heidelberg Univ, Network Aging Res, Heidelberg, Germany.
    Shaffer, Christian M.
    Vanderbilt Univ, Med Ctr, Dept Biomed Informat, Nashville, TN USA.
    Shi, Yuan
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore;Duke NUS Med Sch, Ophthalmol & Visual Sci Acad Clin Program Eye ACP, Singapore, Singapore.
    Smith, Albert V.
    Univ Iceland, Sch Hlth Sci, Fac Med, Reykjavik, Iceland.
    Strauch, Konstantin
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany;LMU, Fac Med, IBE, Chair Genet Epidemiol, Munich, Germany.
    Stumvoll, Michael
    Univ Leipzig, Dept Endocrinol & Nephrol, Leipzig, Germany.
    Sun, Benjamin B.
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England.
    Szymczak, Silke
    Univ Kiel, Univ Hosp Schleswig Holstein, Inst Med Informat & Stat, Kiel, Germany.
    Tai, E-Shyong
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore;Natl Univ Hlth Syst, Singapore, Singapore;Natl Univ Hlth Syst, Singapore, Singapore;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore, Singapore;Duke NUS Med Sch, Singapore, Singapore.
    Tan, Nicholas Y. Q.
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
    Taylor, Kent D.
    Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
    Teren, Andrej
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany;Heart Ctr Leipzig, Leipzig, Germany.
    Tham, Yih-Chung
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
    Thiery, Joachim
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany;Univ Leipzig, Inst Lab Med Clin Chem & Mol Diagnost, Leipzig, Germany.
    Thio, Chris H. L.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.
    Thomsen, Hauke
    German Canc Res Ctr, Div Mol Genet Epidemiol, Heidelberg, Germany.
    Thorsteinsdottir, Unnur
    Amgen Inc, deCODE Genet, Reykjavik, Iceland.
    Tonjes, Anke
    Univ Leipzig, Dept Endocrinol & Nephrol, Leipzig, Germany.
    Tremblay, Johanne
    CHUM, Montreal Univ Hosp Res Ctr, Montreal, PQ, Canada;CRCHUM, Montreal, PQ, Canada.
    Uitterlinden, Andre G.
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
    Van der Harst, Pim
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands;Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands;Netherlands Heart Inst, Durrer Ctr Cardiovasc Res, Utrecht, Netherlands.
    Verweij, Niek
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
    Vogelezang, Suzanne
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus MC, Generat R Study Grp, Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus MC, Dept Pediat, Rotterdam, Netherlands.
    Voelker, Uwe
    DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany;Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany.
    Waldenberger, Melanie
    DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany.
    Wang, Chaolong
    Agcy Sci Technol & Res, Genome Inst Singapore, Singapore, Singapore;Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Publ Hlth, Wuhan, Hubei, Peoples R China.
    Wilson, Otis D.
    Vanderbilt Univ, Med Ctr, Div Nephrol & Hypertens, Nashville, TN USA.
    Wong, Charlene
    Natl Univ Hlth Syst, Singapore, Singapore;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.
    Wong, Tien-Yin
    Natl Univ Hlth Syst, Singapore, Singapore;Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore;Duke NUS Med Sch, Ophthalmol & Visual Sci Acad Clin Program Eye ACP, Singapore, Singapore;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.
    Yang, Qiong
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
    Yasuda, Masayuki
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore;Tohoku Univ, Grad Sch Med, Dept Ophthalmol, Sendai, Miyagi, Japan.
    Akilesh, Shreeram
    Univ Washington, Kidney Res Inst, Seattle, WA 98195 USA;Univ Washington, Med Ctr, Anat Pathol, Seattle, WA 98195 USA.
    Bochud, Murielle
    Univ Lausanne, Ctr Primary Care & Publ Hlth Unisante, Lausanne, Switzerland.
    Boeger, Carsten A.
    Univ Hosp Regensburg, Dept Nephrol, Regensburg, Germany;Kliniken Sudostbayern, Dept Nephrol Diabetol & Rheumatol, Traunstein, Germany.
    Devuyst, Olivier
    Univ Zurich, Inst Physiol, Zurich, Switzerland.
    Edwards, Todd L.
    Vanderbilt Univ, Med Ctr, Dept Med, Div Epidemiol,Vanderbilt Genet Inst, Nashville, TN USA;Vanderbilt Univ, Tennessee Valley H