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  • 251. 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 Cohorts2014Ingår i: American Journal of Nephrology, ISSN 0250-8095, E-ISSN 1421-9670, Vol. 40, nr 5, s. 417-424Artikel i tidskrift (Refereegranskat)
    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.

  • 252.
    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 Interactions2017Ingår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 135, nr 24, s. 2336-2353Artikel i tidskrift (Refereegranskat)
    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.

  • 253.
    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.2019Ingår i: Journal of Exposure Science and Environmental Epidemiology, ISSN 1559-0631, E-ISSN 1559-064X, Vol. 29, nr 2, s. 196-205Artikel i tidskrift (Refereegranskat)
    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.

  • 254.
    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)2015Ingår i: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 82, s. 21-27Artikel i tidskrift (Refereegranskat)
    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.

  • 255.
    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 study2018Ingår i: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 117, s. 196-203Artikel i tidskrift (Refereegranskat)
    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.

  • 256.
    Schmidt, Amand F.
    et al.
    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 study2017Ingår i: The Lancet Diabetes and Endocrinology, ISSN 2213-8587, E-ISSN 2213-8595, Vol. 5, nr 2, s. 97-105Artikel i tidskrift (Refereegranskat)
    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.

  • 257. 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 sensitivity2013Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 56, s. S144-S145Artikel i tidskrift (Övrigt vetenskapligt)
  • 258. 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 obesity2014Ingår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 63, nr 12, s. 4378-4387Artikel i tidskrift (Refereegranskat)
    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.

  • 259.
    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 disease2016Ingår i: Science Translational Medicine, ISSN 1946-6234, E-ISSN 1946-6242, Vol. 8, nr 341, artikel-id 341ra76Artikel i tidskrift (Refereegranskat)
    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.

  • 260.
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    Univ Cambridge, MRC Epidemiol Unit, Cambridge, England..
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    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
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    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..
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    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..
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    Univ Michigan, Dept Biostatist & Ctr Stat Genet, Ann Arbor, MI USA..
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    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
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    Univ Michigan, Dept Biostatist & Ctr Stat Genet, Ann Arbor, MI USA..
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    Univ Michigan, Dept Biostatist & Ctr Stat Genet, Ann Arbor, MI USA..
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    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..
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    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
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    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..
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    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..
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    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..
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    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..
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    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
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    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..
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    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..
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    Univ Nantes, CNRS, Inst Thorax, Ctr Hosp Univ Nantes, Nantes, France..
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    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..
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    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..
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    Karolinska Inst, Dept Med Solna, Cardiovascular Med Unit, Stockholm, Sweden..
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    Univ Iceland, Fac Med, Reykjavik, Iceland.;Landspitali Univ Hosp, Reykjavik, Iceland..
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    Landspitali Univ Hosp, Reykjavik, Iceland..
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    Amgen Inc, DECODE genet, Reykjavik, Iceland..
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    Landspitali Univ Hosp, Reykjavik, Iceland.;Iceland Heart Assoc, Kopavogur, Iceland..
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    Univ Cambridge, MRC Epidemiol Unit, Cambridge, England..
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    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..
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    German Ctr Diabet Res, Neuherberg, Germany..
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    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..
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    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
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    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..
    Lyssenko, Valeriya
    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..
    Couper, David J.
    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..
    Jorgensen, Torben
    Capital Region Denmark, Res Ctr Prevent & Hlth, Copenhagen, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.;Aalborg Univ, Fac Med, Aalborg, Denmark..
    Linneberg, Allan
    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..
    Cornelis, Marilyn C.
    NW Univ Feinberg Sch Med, Dept Prevent Med, Chicago, IL USA..
    Van Dam, Rob M.
    Harvard T H Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Hunter, David J.
    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..
    Kraft, Peter
    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..
    Sun, Qi
    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..
    Edkins, Sarah
    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..
    Sennblad, Bengt
    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 Europeans2017Ingår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 66, nr 11, s. 2888-2902Artikel i tidskrift (Refereegranskat)
    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.

  • 261.
    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 interactions2017Ingår i: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 13, nr 6, artikel-id e1006812Artikel i tidskrift (Refereegranskat)
    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.

  • 262. 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 distribution2015Ingår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 518, nr 7538, s. 187-196Artikel i tidskrift (Refereegranskat)
    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.

  • 263. 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 elderly2016Ingår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 279, nr 2, s. 173-179Artikel i tidskrift (Refereegranskat)
    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.

  • 264.
    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 women2016Ingår i: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 150, s. 59-65Artikel i tidskrift (Refereegranskat)
    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.

  • 265. 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 imputation2015Ingår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 6, artikel-id 8658Artikel i tidskrift (Refereegranskat)
    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.

  • 266.
    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 factors2014Ingår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 275, nr 6, s. 631-639Artikel i tidskrift (Refereegranskat)
    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.

  • 267.
    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 Biology2019Ingår i: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 105, nr 1, s. 15-28Artikel i tidskrift (Refereegranskat)
    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.

  • 268.
    Stenemo, M. Markus
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.