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  • 1. Ahmad, Shafqat
    et al.
    Rukh, Gull
    Varga, Tibor V.
    Ali, Ashfaq
    Kurbasic, Azra
    Shungin, Dmitry
    Ericson, Ulrika
    Koivula, Robert W.
    Chu, Audrey Y.
    Rose, Lynda M.
    Ganna, Andrea
    Qi, Qibin
    Stancakova, Alena
    Sandholt, Camilla H.
    Elks, Cathy E.
    Curhan, Gary
    Jensen, Majken K.
    Tamimi, Rulla M.
    Allin, Kristine H.
    Jorgensen, Torben
    Brage, Soren
    Langenberg, Claudia
    Aadahl, Mette
    Grarup, Niels
    Linneberg, Allan
    Pare, Guillaume
    Magnusson, Patrik K. E.
    Pedersen, Nancy L.
    Boehnke, Michael
    Hamsten, Anders
    Mohlke, Karen L.
    Pasquale, Louis T.
    Pedersen, Oluf
    Scott, Robert A.
    Ridker, Paul M.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Laakso, Markku
    Hansen, Torben
    Qi, Lu
    Wareham, Nicholas J.
    Chasman, Daniel I.
    Hallmans, Goran
    Hu, Frank B.
    Renstrom, Frida
    Orho-Melander, Marju
    Franks, Paul W.
    Gene x Physical Activity Interactions in Obesity: Combined Analysis of 111,421 Individuals of European Ancestry2013In: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 9, no 7, p. e1003607-Article in journal (Refereed)
    Abstract [en]

    Numerous obesity loci have been identified using genome-wide association studies. A UK study indicated that physical activity may attenuate the cumulative effect of 12 of these loci, but replication studies are lacking. Therefore, we tested whether the aggregate effect of these loci is diminished in adults of European ancestry reporting high levels of physical activity. Twelve obesity-susceptibility loci were genotyped or imputed in 111,421 participants. A genetic risk score (GRS) was calculated by summing the BMI-associated alleles of each genetic variant. Physical activity was assessed using self-administered questionnaires. Multiplicative interactions between the GRS and physical activity on BMI were tested in linear and logistic regression models in each cohort, with adjustment for age, age(2), sex, study center (for multicenter studies), and the marginal terms for physical activity and the GRS. These results were combined using meta-analysis weighted by cohort sample size. The meta-analysis yielded a statistically significant GRS x physical activity interaction effect estimate (P-interaction = 0.015). However, a statistically significant interaction effect was only apparent in North American cohorts (n = 39,810, P-interaction = 0.014 vs. n = 71,611, P-interaction = 0.275 for Europeans). In secondary analyses, both the FTO rs1121980 (P-interaction = 0.003) and the SEC16B rs10913469 (P-interaction = 0.025) variants showed evidence of SNP x physical activity interactions. This meta-analysis of 111,421 individuals provides further support for an interaction between physical activity and a GRS in obesity disposition, although these findings hinge on the inclusion of cohorts from North America, indicating that these results are either population-specific or non-causal.

  • 2.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Daniela, Mariosa
    Adami, Hans-Olov
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Lagerros, Ylva Trolle
    Nyren, Olof
    Ye, Weimin
    Bellocco, Rino
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Dose–Response Relationship of Total and Leisure Time Physical Activity to Risk of Heart Failure: a prospective cohort study2014In: Circulation Heart Failure, ISSN 1941-3289, E-ISSN 1941-3297, Vol. 7, no 5, p. 16p. 701-708Article in journal (Refereed)
    Abstract [en]

    Background—The nature of the association between levels of physical activity and risk of heart failure is little known. We investigated nonlinear associations of total and leisure time physical activity with risk of heart failure.

    Methods and Results—In 1997, 39 805 persons without heart failure completed a questionnaire of lifestyle factors and medical history. We used Cox regression models to investigate total (adjusting for education and previous myocardial infarction) and direct (multivariable-adjusted) effects of self-reported total and leisure time physical activity on risk of heart failure of any cause and heart failure of nonischemic origin. Heart failure diagnoses were obtained until December 31, 2010. Higher leisure time physical activity was associated with lower risk of heart failure of any cause; hazard ratio of the total effect of leisure time physical activity was for fifth versus first quintile 0.54; 95% confidence interval was 0.44 to 0.66. The direct effect was similar. High total daily physical activity level was associated with lower risk of heart failure, although the effect was less pronounced than for leisure time physical activity (total effect hazard ratio, 0.81; 95% confidence interval, 0.69–0.95; fifth versus first quintile). A similar direct effect observed.

    Conclusions—Leisure time physical activity was inversely related to risk of developing heart failure in a dose–response fashion. This was reflected in a similar but less pronounced association of total physical activity with risk of heart failure. Only part of the effects appeared to be mediated by traditional risk factors.

  • 3.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Muscle Morphology And Risk Of Cardiovascular Disease2010In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 28, p. E353-E353Article in journal (Other academic)
  • 4.
    Andersen, Kasper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Skeletal muscle morphology and risk of cardiovascular disease in elderly men2015In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 22, no 2, p. 231-239Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    While it is well known that physical inactivity is a major risk factor for cardiovascular disease, there is still a search for the mechanisms by which exercise exerts its positive effect. Skeletal muscle fibre type can be affected to some extent by exercise, and different fibre types possess different anti-inflammatory and glucometabolic properties that may influence cardiovascular disease risk.

    DESIGN:

    Population-based cohort study.

    METHODS:

    We investigated relations of skeletal muscle morphology to risk of cardiovascular events in a sample of 466 71-year-old men without cardiovascular disease, of which 295 were physically active (strenuous physical activity at least 3 h/week).

    RESULTS:

    During a median of 13.1 years of follow up, 173 major cardiovascular events occurred. Among physically active men, 10% higher proportion of type-I (slow-twitch oxidative) fibres was associated with a hazard ratio (HR) of 0.84 (95% confidence interval 0.74-0.95) for cardiovascular events, and 10% higher proportion of type-IIx (fast-twitch glycolytic) fibres was associated with a HR of 1.24 (1.06-1.45), adjusting for age. Similar results were observed in several sets of multivariable-adjusted models. No association of muscle fibre type with risk of cardiovascular events was observed among physically inactive men.

    CONCLUSIONS:

    Higher skeletal muscle proportion of type-I fibres was associated with lower risk of cardiovascular events and a higher proportion of type-IIx fibres was associated with higher risk of cardiovascular events. These relations were only observed in physically active men. Skeletal muscle fibre composition may be a mediator of the protective effects of exercise against cardiovascular disease.

  • 5.
    Arefalk, Gabriel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hergens, M. P.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ye, W.
    Nyrén, O.
    Lambe, M.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Smokeless Tobacco (Snus) And Risk Of Heart Failure In Two Swedish Cohorts2010In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 28, p. E48-E49Article in journal (Other academic)
  • 6.
    Arefalk, Gabriel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Hergens, Maria-Pia
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ye, Weimin
    Nyrén, Olof
    Lambe, Mats
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Smokeless tobacco (snus) and risk of heart failure: results from two Swedish cohorts2012In: European Journal of Cardiovascular Prevention & Rehabilitation, ISSN 1741-8267, E-ISSN 1741-8275, Vol. 19, no 5, p. 1120-1127Article in journal (Refereed)
    Abstract [en]

    Background:

    Oral moist snuff (snus) is discussed as a safer alternative to smoking, and its use is increasing. Based on its documented effect on blood pressure, we hypothesized that use of snus increases the risk of heart failure.

    Design:

    Two independent Swedish prospective cohorts; the Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based sample of 1076 elderly men, and the Construction Workers Cohort (CWC), a sample of 118,425 never-smoking male construction workers.

    Methods:

    Cox proportional hazards models were used to investigate possible associations of snus use with risk of a first hospitalization for heart failure.

    Results:

    In ULSAM, 95 men were hospitalized for heart failure, during a median follow up of 8.9 years. In a model adjusted for established risk factors including past and present smoking exposure, current snus use was associated with a higher risk of heart failure [hazard ratio (HR) 2.08, 95% confidence interval (CI) 1.03-4.22] relative to non-use. Snus use was particularly associated with risk of non-ischaemic heart failure (HR 2.55, 95% CI 1.12-5.82). In CWC, 545 men were hospitalized for heart failure, during a median follow up of 18 years. In multivariable-adjusted models, current snus use was moderately associated with a higher risk of heart failure (HR 1.28, 95% CI 1.00-1.64) and non-ischaemic heart failure (HR 1.28, 95% CI 0.97-1.68) relative to never tobacco use.

    Conclusion:

    Data from two independent cohorts suggest that use of snus may be associated with a higher risk of heart failure.

  • 7. Arking, Dan E
    et al.
    Pulit, Sara L
    Crotti, Lia
    van der Harst, Pim
    Munroe, Patricia B
    Koopmann, Tamara T
    Sotoodehnia, Nona
    Rossin, Elizabeth J
    Morley, Michael
    Wang, Xinchen
    Johnson, Andrew D
    Lundby, Alicia
    Gudbjartsson, Daníel F
    Noseworthy, Peter A
    Eijgelsheim, Mark
    Bradford, Yuki
    Tarasov, Kirill V
    Dörr, Marcus
    Müller-Nurasyid, Martina
    Lahtinen, Annukka M
    Nolte, Ilja M
    Smith, Albert Vernon
    Bis, Joshua C
    Isaacs, Aaron
    Newhouse, Stephen J
    Evans, Daniel S
    Post, Wendy S
    Waggott, Daryl
    Lyytikäinen, Leo-Pekka
    Hicks, Andrew A
    Eisele, Lewin
    Ellinghaus, David
    Hayward, Caroline
    Navarro, Pau
    Ulivi, Sheila
    Tanaka, Toshiko
    Tester, David J
    Chatel, Stéphanie
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kumari, Meena
    Morris, Richard W
    Naluai, Asa T
    Padmanabhan, Sandosh
    Kluttig, Alexander
    Strohmer, Bernhard
    Panayiotou, Andrie G
    Torres, Maria
    Knoflach, Michael
    Hubacek, Jaroslav A
    Slowikowski, Kamil
    Raychaudhuri, Soumya
    Kumar, Runjun D
    Harris, Tamara B
    Launer, Lenore J
    Shuldiner, Alan R
    Alonso, Alvaro
    Bader, Joel S
    Ehret, Georg
    Huang, Hailiang
    Kao, W H Linda
    Strait, James B
    Macfarlane, Peter W
    Brown, Morris
    Caulfield, Mark J
    Samani, Nilesh J
    Kronenberg, Florian
    Willeit, Johann
    Smith, J Gustav
    Greiser, Karin H
    Meyer Zu Schwabedissen, Henriette
    Werdan, Karl
    Carella, Massimo
    Zelante, Leopoldo
    Heckbert, Susan R
    Psaty, Bruce M
    Rotter, Jerome I
    Kolcic, Ivana
    Polašek, Ozren
    Wright, Alan F
    Griffin, Maura
    Daly, Mark J
    Arnar, David O
    Hólm, Hilma
    Thorsteinsdottir, Unnur
    Denny, Joshua C
    Roden, Dan M
    Zuvich, Rebecca L
    Emilsson, Valur
    Plump, Andrew S
    Larson, Martin G
    O'Donnell, Christopher J
    Yin, Xiaoyan
    Bobbo, Marco
    D'Adamo, Adamo P
    Iorio, Annamaria
    Sinagra, Gianfranco
    Carracedo, Angel
    Cummings, Steven R
    Nalls, Michael A
    Jula, Antti
    Kontula, Kimmo K
    Marjamaa, Annukka
    Oikarinen, Lasse
    Perola, Markus
    Porthan, Kimmo
    Erbel, Raimund
    Hoffmann, Per
    Jöckel, Karl-Heinz
    Kälsch, Hagen
    Nöthen, Markus M
    den Hoed, Marcel
    Loos, Ruth J F
    Thelle, Dag S
    Gieger, Christian
    Meitinger, Thomas
    Perz, Siegfried
    Peters, Annette
    Prucha, Hanna
    Sinner, Moritz F
    Waldenberger, Melanie
    de Boer, Rudolf A
    Franke, Lude
    van der Vleuten, Pieter A
    Beckmann, Britt Maria
    Martens, Eimo
    Bardai, Abdennasser
    Hofman, Nynke
    Wilde, Arthur A M
    Behr, Elijah R
    Dalageorgou, Chrysoula
    Giudicessi, John R
    Medeiros-Domingo, Argelia
    Barc, Julien
    Kyndt, Florence
    Probst, Vincent
    Ghidoni, Alice
    Insolia, Roberto
    Hamilton, Robert M
    Scherer, Stephen W
    Brandimarto, Jeffrey
    Margulies, Kenneth
    Moravec, Christine E
    Greco M, Fabiola Del
    Fuchsberger, Christian
    O'Connell, Jeffrey R
    Lee, Wai K
    Watt, Graham C M
    Campbell, Harry
    Wild, Sarah H
    El Mokhtari, Nour E
    Frey, Norbert
    Asselbergs, Folkert W
    Mateo Leach, Irene
    Navis, Gerjan
    van den Berg, Maarten P
    van Veldhuisen, Dirk J
    Kellis, Manolis
    Krijthe, Bouwe P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Franco, Oscar H
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hofman, Albert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kors, Jan A
    Uitterlinden, André G
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Witteman, Jacqueline C M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kedenko, Lyudmyla
    Lamina, Claudia
    Oostra, Ben A
    Abecasis, Gonçalo R
    Lakatta, Edward G
    Mulas, Antonella
    Orrú, Marco
    Schlessinger, David
    Uda, Manuela
    Markus, Marcello R P
    Völker, Uwe
    Snieder, Harold
    Spector, Timothy D
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Sundström, Johan
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kivimaki, Mika
    Kähönen, Mika
    Mononen, Nina
    Raitakari, Olli T
    Viikari, Jorma S
    Adamkova, Vera
    Kiechl, Stefan
    Brion, Maria
    Nicolaides, Andrew N
    Paulweber, Bernhard
    Haerting, Johannes
    Dominiczak, Anna F
    Nyberg, Fredrik
    Whincup, Peter H
    Hingorani, Aroon D
    Schott, Jean-Jacques
    Bezzina, Connie R
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ferrucci, Luigi
    Gasparini, Paolo
    Wilson, James F
    Rudan, Igor
    Franke, Andre
    Mühleisen, Thomas W
    Pramstaller, Peter P
    Lehtimäki, Terho J
    Paterson, Andrew D
    Parsa, Afshin
    Liu, Yongmei
    van Duijn, Cornelia M
    Siscovick, David S
    Gudnason, Vilmundur
    Jamshidi, Yalda
    Salomaa, Veikko
    Felix, Stephan B
    Sanna, Serena
    Ritchie, Marylyn D
    Stricker, Bruno H
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Stefansson, Kari
    Boyer, Laurie A
    Cappola, Thomas P
    Olsen, Jesper V
    Lage, Kasper
    Schwartz, Peter J
    Kääb, Stefan
    Chakravarti, Aravinda
    Ackerman, Michael J
    Pfeufer, Arne
    de Bakker, Paul I W
    Newton-Cheh, Christopher
    Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.2014In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 46, no 8, p. 826-836Article in journal (Refereed)
    Abstract [en]

    The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.

  • 8. Arnlov, Johan
    et al.
    Carlsson, Axel C.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Larsson, Tobias E.
    Serum FGF23 and Risk of Cardiovascular Events in Relation to Mineral Metabolism and Cardiovascular Pathology2013In: American Society of Nephrology. Clinical Journal, ISSN 1555-9041, E-ISSN 1555-905X, Vol. 8, no 5, p. 781-786Article in journal (Refereed)
    Abstract [en]

    Background and objectives Circulating fibroblast growth factor-23 is associated with adverse cardiovascular outcomes in CKD and non-CKD individuals, but the underlying mechanism remains unclear. This study tested whether this association is independent of mineral metabolism and indices of subclinical cardiovascular pathology. Design, setting, participants, & measurements The prospective association between fibroblast growth factor-23 and major cardiovascular events (a composite of hospital-treated myocardial infarction, hospital-treated stroke, or all-cause mortality) was investigated in the community-based Prospective Investigation of the Vasculature in Uppsala Seniors (n=973; mean age=70 years, 50% women) using multivariate logistic regression. Subjects were recruited between January of 2001 and June of 2004. Results During follow-up (median=5.1 years), 112 participants suffered a major cardiovascular event. In logistic regression models adjusted for age, sex, and estimated GFR, higher fibroblast growth factor-23 was associated with increased risk for major cardiovascular events (odds ratio for tertiles 2 and 3 versus tertile 1=1.92, 95% confidence interval=1.19-3.09, P<0.01). After additional adjustments in the model, adding established cardiovascular risk factors, confounders of mineral metabolism (calcium, phosphate, parathyroid hormone, and 25 (OH)-vitamin D), and indices of subclinical pathology (flow-mediated vasodilation, endothelial-dependent and -independent vasodilation, arterial stiffness, and atherosclerosis and left ventricular mass) attenuated this relationship, but it remained significant (odds ratio for tertiles 2 and 3 versus tertile 1=1.69, 95% confidence interval=1.01-2.82, P<0.05). Conclusions Fibroblast growth factor-23 is an independent predictor of cardiovascular events in the community, even after accounting for mineral metabolism abnormalities and subclinical cardiovascular damage. Circulating fibroblast growth factor-23 may reflect novel and important aspects of cardiovascular risk yet to be unraveled.

  • 9.
    Atabaki-Pasdar, Naeimeh
    et al.
    Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, SE-20502 Malmo, Sweden..
    Ohlsson, Mattias
    Lund Univ, Dept Astron & Theoret Phys, Computat Biol & Biol Phys Unit, Lund, Sweden..
    Shungin, Dmitry
    Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, SE-20502 Malmo, Sweden..
    Kurbasic, Azra
    Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, SE-20502 Malmo, Sweden..
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Pearson, Ewan R.
    Univ Dundee, Med Res Inst, Div Cardiovasc & Diabet Med, Dundee, Scotland..
    Ali, Ashfaq
    Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, SE-20502 Malmo, Sweden..
    Franks, Paul W.
    Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, SE-20502 Malmo, Sweden.;Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.;Harvard Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA..
    Statistical power considerations in genotype-based recall randomized controlled trials2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 37307Article in journal (Refereed)
    Abstract [en]

    Randomized controlled trials (RCT) are often underpowered for validating gene-treatment interactions. Using published data from the Diabetes Prevention Program (DPP), we examined power in conventional and genotype-based recall (GBR) trials. We calculated sample size and statistical power for genemetformin interactions (vs. placebo) using incidence rates, gene-drug interaction effect estimates and allele frequencies reported in the DPP for the rs8065082 SLC47A1 variant, a metformin transported encoding locus. We then calculated statistical power for interactions between genetic risk scores (GRS), metformin treatment and intensive lifestyle intervention (ILI) given a range of sampling frames, clinical trial sample sizes, interaction effect estimates, and allele frequencies; outcomes were type 2 diabetes incidence (time-to-event) and change in small LDL particles (continuous outcome). Thereafter, we compared two recruitment frameworks: GBR (participants recruited from the extremes of a GRS distribution) and conventional sampling (participants recruited without explicit emphasis on genetic characteristics). We further examined the influence of outcome measurement error on statistical power. Under most simulated scenarios, GBR trials have substantially higher power to observe gene-drug and gene-lifestyle interactions than same-sized conventional RCTs. GBR trials are becoming popular for validation of gene-treatment interactions; our analyses illustrate the strengths and weaknesses of this design.

  • 10.
    Benedict, Christian
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Axelsson, Tomas
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Söderberg, Stefan
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    The fat mass and obesity-associated gene (FTO) is linked to higher plasma levels of the hunger hormone ghrelin and lower serum levels of the satiety hormone leptin in older adults2014In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 63, no 11, p. 3955-3959Article in journal (Refereed)
    Abstract [en]

    The mechanisms through which common polymorphisms in the fat mass and obesity-associated gene (FTO) drive the development of obesity in humans are poorly understood. By using C: ross-sectional data from 985 elderly (50% females) who participated at age 70 years in the Prospective Investigation of the Vasculature in Uppsala Seniors, circulating levels of ghrelin and leptin were measured after an overnight fast. In addition, subjects were genotyped for FTO rs17817449 (AA, n=345 (35%); AC/CA, n=481 (48.8%); CC, n=159 (16.1%). Linear regression analyses controlling for sex, self-reported physical activity level, fasting plasma glucose, and body mass index were utilized. A positive relationship between the number of FTO C risk alleles and plasma ghrelin levels was found (P=0.005; relative plasma ghrelin difference between CC and AA carriers = ∼9%). In contrast, serum levels of the satiety enhancing hormone leptin were inversely linked to the number of FTO C risk alleles (P=0.001; relative serum leptin difference between CC and AA carriers = ∼11%). These associations were also found when controlling for waist circumference. The present findings suggest that FTO may facilitate weight gain in humans by shifting the endocrine balance from the satiety hormone leptin toward the hunger promoting hormone ghrelin.

  • 11. Berndt, Sonja I.
    et al.
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Maegi, Reedik
    Ganna, Andrea
    Wheeler, Eleanor
    Feitosa, Mary F.
    Justice, Anne E.
    Monda, Keri L.
    Croteau-Chonka, Damien C.
    Day, Felix R.
    Esko, Tonu
    Fall, Tove
    Ferreira, Teresa
    Gentilini, Davide
    Jackson, Anne U.
    Luan, Jian'an
    Randall, Joshua C.
    Vedantam, Sailaja
    Willer, Cristen J.
    Winkler, Thomas W.
    Wood, Andrew R.
    Workalemahu, Tsegaselassie
    Hu, Yi-Juan
    Lee, Sang Hong
    Liang, Liming
    Lin, Dan-Yu
    Min, Josine L.
    Neale, Benjamin M.
    Thorleifsson, Gudmar
    Yang, Jian
    Albrecht, Eva
    Amin, Najaf
    Bragg-Gresham, Jennifer L.
    Cadby, Gemma
    den Heijer, Martin
    Eklund, Niina
    Fischer, Krista
    Goel, Anuj
    Hottenga, Jouke-Jan
    Huffman, Jennifer E.
    Jarick, Ivonne
    Johansson, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Johnson, Toby
    Kanoni, Stavroula
    Kleber, Marcus E.
    Koenig, Inke R.
    Kristiansson, Kati
    Kutalik, Zoltn
    Lamina, Claudia
    Lecoeur, Cecile
    Li, Guo
    Mangino, Massimo
    McArdle, Wendy L.
    Medina-Gomez, Carolina
    Mueller-Nurasyid, Martina
    Ngwa, Julius S.
    Nolte, Ilja M.
    Paternoster, Lavinia
    Pechlivanis, Sonali
    Perola, Markus
    Peters, Marjolein J.
    Preuss, Michael
    Rose, Lynda M.
    Shi, Jianxin
    Shungin, Dmitry
    Smith, Albert Vernon
    Strawbridge, Rona J.
    Surakka, Ida
    Teumer, Alexander
    Trip, Mieke D.
    Tyrer, Jonathan
    Van Vliet-Ostaptchouk, Jana V.
    Vandenput, Liesbeth
    Waite, Lindsay L.
    Zhao, Jing Hua
    Absher, Devin
    Asselbergs, Folkert W.
    Atalay, Mustafa
    Attwood, Antony P.
    Balmforth, Anthony J.
    Basart, Hanneke
    Beilby, John
    Bonnycastle, Lori L.
    Brambilla, Paolo
    Bruinenberg, Marcel
    Campbell, Harry
    Chasman, Daniel I.
    Chines, Peter S.
    Collins, Francis S.
    Connell, John M.
    Cookson, William O.
    de Faire, Ulf
    de Vegt, Femmie
    Dei, Mariano
    Dimitriou, Maria
    Edkins, Sarah
    Estrada, Karol
    Evans, David M.
    Farrall, Martin
    Ferrario, Marco M.
    Ferrieres, Jean
    Franke, Lude
    Frau, Francesca
    Gejman, Pablo V.
    Grallert, Harald
    Groenberg, Henrik
    Gudnason, Vilmundur
    Hall, Alistair S.
    Hall, Per
    Hartikainen, Anna-Liisa
    Hayward, Caroline
    Heard-Costa, Nancy L.
    Heath, Andrew C.
    Hebebrand, Johannes
    Homuth, Georg
    Hu, Frank B.
    Hunt, Sarah E.
    Hyppoenen, Elina
    Iribarren, Carlos
    Jacobs, Kevin B.
    Jansson, John-Olov
    Jula, Antti
    Kahonen, Mika
    Kathiresan, Sekar
    Kee, Frank
    Khaw, Kay-Tee
    Kivimaki, Mika
    Koenig, Wolfgang
    Kraja, Aldi T.
    Kumari, Meena
    Kuulasmaa, Kari
    Kuusisto, Johanna
    Laitinen, Jaana H.
    Lakka, Timo A.
    Langenberg, Claudia
    Launer, Lenore J.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lindstrom, Jaana
    Liu, Jianjun
    Liuzzi, Antonio
    Lokki, Marja-Liisa
    Lorentzon, Mattias
    Madden, Pamela A.
    Magnusson, Patrik K.
    Manunta, Paolo
    Marek, Diana
    Maerz, Winfried
    Leach, Irene Mateo
    McKnight, Barbara
    Medland, Sarah E.
    Mihailov, Evelin
    Milani, Lili
    Montgomery, Grant W.
    Mooser, Vincent
    Muehleisen, Thomas W.
    Munroe, Patricia B.
    Musk, Arthur W.
    Narisu, Narisu
    Navis, Gerjan
    Nicholson, George
    Nohr, Ellen A.
    Ong, Ken K.
    Oostra, Ben A.
    Palmer, Colin N. A.
    Palotie, Aarno
    Peden, John F.
    Pedersen, Nancy
    Peters, Annette
    Polasek, Ozren
    Pouta, Anneli
    Pramstaller, Peter P.
    Prokopenko, Inga
    Puetter, Carolin
    Radhakrishnan, Aparna
    Raitakari, Olli
    Rendon, Augusto
    Rivadeneira, Fernando
    Rudan, Igor
    Saaristo, Timo E.
    Sambrook, Jennifer G.
    Sanders, Alan R.
    Sanna, Serena
    Saramies, Jouko
    Schipf, Sabine
    Schreiber, Stefan
    Schunkert, Heribert
    Shin, So-Youn
    Signorini, Stefano
    Sinisalo, Juha
    Skrobek, Boris
    Soranzo, Nicole
    Stancakova, Alena
    Stark, Klaus
    Stephens, Jonathan C.
    Stirrups, Kathleen
    Stolk, Ronald P.
    Stumvoll, Michael
    Swift, Amy J.
    Theodoraki, Eirini V.
    Thorand, Barbara
    Tregouet, David-Alexandre
    Tremoli, Elena
    Van der Klauw, Melanie M.
    van Meurs, Joyce B. J.
    Vermeulen, Sita H.
    Viikari, Jorma
    Virtamo, Jarmo
    Vitart, Veronique
    Waeber, Gerard
    Wang, Zhaoming
    Widen, Elisabeth
    Wild, Sarah H.
    Willemsen, Gonneke
    Winkelmann, Bernhard R.
    Witteman, Jacqueline C. M.
    Wolffenbuttel, Bruce H. R.
    Wong, Andrew
    Wright, Alan F.
    Zillikens, M. Carola
    Amouyel, Philippe
    Boehm, Bernhard O.
    Boerwinkle, Eric
    Boomsma, Dorret I.
    Caulfield, Mark J.
    Chanock, Stephen J.
    Cupples, L. Adrienne
    Cusi, Daniele
    Dedoussis, George V.
    Erdmann, Jeanette
    Eriksson, Johan G.
    Franks, Paul W.
    Froguel, Philippe
    Gieger, Christian
    Gyllensten, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics.
    Hamsten, Anders
    Harris, Tamara B.
    Hengstenberg, Christian
    Hicks, Andrew A.
    Hingorani, Aroon
    Hinney, Anke
    Hofman, Albert
    Hovingh, Kees G.
    Hveem, Kristian
    Illig, Thomas
    Jarvelin, Marjo-Riitta
    Joeckel, Karl-Heinz
    Keinanen-Kiukaanniemi, Sirkka M.
    Kiemeney, Lambertus A.
    Kuh, Diana
    Laakso, Markku
    Lehtimaki, Terho
    Levinson, Douglas F.
    Martin, Nicholas G.
    Metspalu, Andres
    Morris, Andrew D.
    Nieminen, Markku S.
    Njolstad, Inger
    Ohlsson, Claes
    Oldehinkel, Albertine J.
    Ouwehand, Willem H.
    Palmer, Lyle J.
    Penninx, Brenda
    Power, Chris
    Province, Michael A.
    Psaty, Bruce M.
    Qi, Lu
    Rauramaa, Rainer
    Ridker, Paul M.
    Ripatti, Samuli
    Salomaa, Veikko
    Samani, Nilesh J.
    Snieder, Harold
    Sorensen, Thorkild I. A.
    Spector, Timothy D.
    Stefansson, Kari
    Tonjes, Anke
    Tuomilehto, Jaakko
    Uitterlinden, Andre G.
    Uusitupa, Matti
    van der Harst, Pim
    Vollenweider, Peter
    Wallaschofski, Henri
    Wareham, Nicholas J.
    Watkins, Hugh
    Wichmann, H-Erich
    Wilson, James F.
    Abecasis, Goncalo R.
    Assimes, Themistocles L.
    Barroso, Ines
    Boehnke, Michael
    Borecki, Ingrid B.
    Deloukas, Panos
    Fox, Caroline S.
    Frayling, Timothy
    Groop, Leif C.
    Haritunian, Talin
    Heid, Iris M.
    Hunter, David
    Kaplan, Robert C.
    Karpe, Fredrik
    Moffatt, Miriam F.
    Mohlke, Karen L.
    O'Connell, Jeffrey R.
    Pawitan, Yudi
    Schadt, Eric E.
    Schlessinger, David
    Steinthorsdottir, Valgerdur
    Strachan, David P.
    Thorsteinsdottir, Unnur
    van Duijn, Cornelia M.
    Visscher, Peter M.
    Di Blasio, Anna Maria
    Hirschhorn, Joel N.
    Lindgren, Cecilia M.
    Morris, Andrew P.
    Meyre, David
    Scherag, Andr
    McCarthy, Mark I.
    Speliotes, Elizabeth K.
    North, Kari E.
    Loos, Ruth J. F.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture2013In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 45, no 5, p. 501-U69Article in journal (Refereed)
    Abstract [en]

    Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

  • 12. Berndt, Sonja I.
    et al.
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Maegi, Reedik
    Ganna, Andrea
    Wheeler, Eleanor
    Feitosa, Mary F.
    Justice, Anne E.
    Monda, Keri L.
    Croteau-Chonka, Damien C.
    Day, Felix R.
    Esko, Tonu
    Fall, Tove
    Ferreira, Teresa
    Gentilini, Davide
    Jackson, Anne U.
    Luan, Jian'an
    Randall, Joshua C.
    Vedantam, Sailaja
    Willer, Cristen J.
    Winkler, Thomas W.
    Wood, Andrew R.
    Workalemahu, Tsegaselassie
    Hu, Yi-Juan
    Lee, Sang Hong
    Liang, Liming
    Lin, Dan-Yu
    Min, Josine L.
    Neale, Benjamin M.
    Thorleifsson, Gudmar
    Yang, Jian
    Albrecht, Eva
    Amin, Najaf
    Bragg-Gresham, Jennifer L.
    Cadby, Gemma
    den Heijer, Martin
    Eklund, Niina
    Fischer, Krista
    Goel, Anuj
    Hottenga, Jouke-Jan
    Huffman, Jennifer E.
    Jarick, Ivonne
    Johansson, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Johnson, Toby
    Kanoni, Stavroula
    Kleber, Marcus E.
    Koenig, Inke R.
    Kristiansson, Kati
    Kutalik, Zoltn
    Lamina, Claudia
    Lecoeur, Cecile
    Li, Guo
    Mangino, Massimo
    McArdle, Wendy L.
    Medina-Gomez, Carolina
    Mueller-Nurasyid, Martina
    Ngwa, Julius S.
    Nolte, Ilja M.
    Paternoster, Lavinia
    Pechlivanis, Sonali
    Perola, Markus
    Peters, Marjolein J.
    Preuss, Michael
    Rose, Lynda M.
    Shi, Jianxin
    Shungin, Dmitry
    Smith, Albert Vernon
    Strawbridge, Rona J.
    Surakka, Ida
    Teumer, Alexander
    Trip, Mieke D.
    Tyrer, Jonathan
    Van Vliet-Ostaptchouk, Jana V.
    Vandenput, Liesbeth
    Waite, Lindsay L.
    Zhao, Jing Hua
    Absher, Devin
    Asselbergs, Folkert W.
    Atalay, Mustafa
    Attwood, Antony P.
    Balmforth, Anthony J.
    Basart, Hanneke
    Beilby, John
    Bonnycastle, Lori L.
    Brambilla, Paolo
    Bruinenberg, Marcel
    Campbell, Harry
    Chasman, Daniel I.
    Chines, Peter S.
    Collins, Francis S.
    Connell, John M.
    Cookson, William O.
    de Faire, Ulf
    de Vegt, Femmie
    Dei, Mariano
    Dimitriou, Maria
    Edkins, Sarah
    Estrada, Karol
    Evans, David M.
    Farrall, Martin
    Ferrario, Marco M.
    Ferrieres, Jean
    Franke, Lude
    Frau, Francesca
    Gejman, Pablo V.
    Grallert, Harald
    Groenberg, Henrik
    Gudnason, Vilmundur
    Hall, Alistair S.
    Hall, Per
    Hartikainen, Anna-Liisa
    Hayward, Caroline
    Heard-Costa, Nancy L.
    Heath, Andrew C.
    Hebebrand, Johannes
    Homuth, Georg
    Hu, Frank B.
    Hunt, Sarah E.
    Hyppoenen, Elina
    Iribarren, Carlos
    Jacobs, Kevin B.
    Jansson, John-Olov
    Jula, Antti
    Kahonen, Mika
    Kathiresan, Sekar
    Kee, Frank
    Khaw, Kay-Tee
    Kivimaki, Mika
    Koenig, Wolfgang
    Kraja, Aldi T.
    Kumari, Meena
    Kuulasmaa, Kari
    Kuusisto, Johanna
    Laitinen, Jaana H.
    Lakka, Timo A.
    Langenberg, Claudia
    Launer, Lenore J.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lindstrom, Jaana
    Liu, Jianjun
    Liuzzi, Antonio
    Lokki, Marja-Liisa
    Lorentzon, Mattias
    Madden, Pamela A.
    Magnusson, Patrik K.
    Manunta, Paolo
    Marek, Diana
    Maerz, Winfried
    Leach, Irene Mateo
    McKnight, Barbara
    Medland, Sarah E.
    Mihailov, Evelin
    Milani, Lili
    Montgomery, Grant W.
    Mooser, Vincent
    Muehleisen, Thomas W.
    Munroe, Patricia B.
    Musk, Arthur W.
    Narisu, Narisu
    Navis, Gerjan
    Nicholson, George
    Nohr, Ellen A.
    Ong, Ken K.
    Oostra, Ben A.
    Palmer, Colin N. A.
    Palotie, Aarno
    Peden, John F.
    Pedersen, Nancy
    Peters, Annette
    Polasek, Ozren
    Pouta, Anneli
    Pramstaller, Peter P.
    Prokopenko, Inga
    Puetter, Carolin
    Radhakrishnan, Aparna
    Raitakari, Olli
    Rendon, Augusto
    Rivadeneira, Fernando
    Rudan, Igor
    Saaristo, Timo E.
    Sambrook, Jennifer G.
    Sanders, Alan R.
    Sanna, Serena
    Saramies, Jouko
    Schipf, Sabine
    Schreiber, Stefan
    Schunkert, Heribert
    Shin, So-Youn
    Signorini, Stefano
    Sinisalo, Juha
    Skrobek, Boris
    Soranzo, Nicole
    Stancakova, Alena
    Stark, Klaus
    Stephens, Jonathan C.
    Stirrups, Kathleen
    Stolk, Ronald P.
    Stumvoll, Michael
    Swift, Amy J.
    Theodoraki, Eirini V.
    Thorand, Barbara
    Tregouet, David-Alexandre
    Tremoli, Elena
    Van der Klauw, Melanie M.
    van Meurs, Joyce B. J.
    Vermeulen, Sita H.
    Viikari, Jorma
    Virtamo, Jarmo
    Vitart, Veronique
    Waeber, Gerard
    Wang, Zhaoming
    Widen, Elisabeth
    Wild, Sarah H.
    Willemsen, Gonneke
    Winkelmann, Bernhard R.
    Witteman, Jacqueline C. M.
    Wolffenbuttel, Bruce H. R.
    Wong, Andrew
    Wright, Alan F.
    Zillikens, M. Carola
    Amouyel, Philippe
    Boehm, Bernhard O.
    Boerwinkle, Eric
    Boomsma, Dorret I.
    Caulfield, Mark J.
    Chanock, Stephen J.
    Cupples, L. Adrienne
    Cusi, Daniele
    Dedoussis, George V.
    Erdmann, Jeanette
    Eriksson, Johan G.
    Franks, Paul W.
    Froguel, Philippe
    Gieger, Christian
    Gyllensten, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics.
    Hamsten, Anders
    Harris, Tamara B.
    Hengstenberg, Christian
    Hicks, Andrew A.
    Hingorani, Aroon
    Hinney, Anke
    Hofman, Albert
    Hovingh, Kees G.
    Hveem, Kristian
    Illig, Thomas
    Jarvelin, Marjo-Riitta
    Joeckel, Karl-Heinz
    Keinanen-Kiukaanniemi, Sirkka M.
    Kiemeney, Lambertus A.
    Kuh, Diana
    Laakso, Markku
    Lehtimaki, Terho
    Levinson, Douglas F.
    Martin, Nicholas G.
    Metspalu, Andres
    Morris, Andrew D.
    Nieminen, Markku S.
    Njolstad, Inger
    Ohlsson, Claes
    Oldehinkel, Albertine J.
    Ouwehand, Willem H.
    Palmer, Lyle J.
    Penninx, Brenda
    Power, Chris
    Province, Michael A.
    Psaty, Bruce M.
    Qi, Lu
    Rauramaa, Rainer
    Ridker, Paul M.
    Ripatti, Samuli
    Salomaa, Veikko
    Samani, Nilesh J.
    Snieder, Harold
    Sorensen, Thorkild I. A.
    Spector, Timothy D.
    Stefansson, Kari
    Tonjes, Anke
    Tuomilehto, Jaakko
    Uitterlinden, Andre G.
    Uusitupa, Matti
    van der Harst, Pim
    Vollenweider, Peter
    Wallaschofski, Henri
    Wareham, Nicholas J.
    Watkins, Hugh
    Wichmann, H-Erich
    Wilson, James F.
    Abecasis, Goncalo R.
    Assimes, Themistocles L.
    Barroso, Ines
    Boehnke, Michael
    Borecki, Ingrid B.
    Deloukas, Panos
    Fox, Caroline S.
    Frayling, Timothy
    Groop, Leif C.
    Haritunian, Talin
    Heid, Iris M.
    Hunter, David
    Kaplan, Robert C.
    Karpe, Fredrik
    Moffatt, Miriam F.
    Mohlke, Karen L.
    O'Connell, Jeffrey R.
    Pawitan, Yudi
    Schadt, Eric E.
    Schlessinger, David
    Steinthorsdottir, Valgerdur
    Strachan, David P.
    Thorsteinsdottir, Unnur
    van Duijn, Cornelia M.
    Visscher, Peter M.
    Di Blasio, Anna Maria
    Hirschhorn, Joel N.
    Lindgren, Cecilia M.
    Morris, Andrew P.
    Meyre, David
    Scherag, Andr
    McCarthy, Mark I.
    Speliotes, Elizabeth K.
    North, Kari E.
    Loos, Ruth J. F.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture2013In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 45, no 5, p. 501-U69Article in journal (Refereed)
    Abstract [en]

    Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

  • 13. Bolton, Jennifer L.
    et al.
    Hayward, Caroline
    Direk, Nese
    Lewis, John G.
    Hammond, Geoffrey L.
    Hill, Lesley A.
    Anderson, Anna
    Huffman, Jennifer
    Wilson, James F.
    Campbell, Harry
    Rudan, Igor
    Wright, Alan
    Hastie, Nicholas
    Wild, Sarah H.
    Velders, Fleur P.
    Hofman, Albert
    Uitterlinden, Andre G.
    Lahti, Jari
    Raikkonen, Katri
    Kajantie, Eero
    Widen, Elisabeth
    Palotie, Aarno
    Eriksson, Johan G.
    Kaakinen, Marika
    Jarvelin, Marjo-Riitta
    Timpson, Nicholas J.
    Smith, George Davey
    Ring, Susan M.
    Evans, David M.
    St Pourcain, Beate
    Tanaka, Toshiko
    Milaneschi, Yuri
    Bandinelli, Stefania
    Ferrucci, Luigi
    van der Harst, Pim
    Rosmalen, Judith G. M.
    Bakker, Stephen J. L.
    Verweij, Niek
    Dullaart, Robin P. F.
    Mahajan, Anubha
    Lindgren, Cecilia M.
    Morris, Andrew
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Anderson, Laura N.
    Pennell, Craig E.
    Lye, Stephen J.
    Matthews, Stephen G.
    Eriksson, Joel
    Mellstrom, Dan
    Ohlsson, Claes
    Price, Jackie F.
    Strachan, Mark W. J.
    Reynolds, Rebecca M.
    Tiemeier, Henning
    Walker, Brian R.
    Genome Wide Association Identifies Common Variants at the SERPINA6/SERPINA1 Locus Influencing Plasma Cortisol and Corticosteroid Binding Globulin2014In: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 10, no 7Article in journal (Refereed)
    Abstract [en]

    Variation in plasma levels of cortisol, an essential hormone in the stress response, is associated in population-based studies with cardio-metabolic, inflammatory and neuro-cognitive traits and diseases. Heritability of plasma cortisol is estimated at 30-60% but no common genetic contribution has been identified. The CORtisol NETwork (CORNET) consortium undertook genome wide association meta-analysis for plasma cortisol in 12,597 Caucasian participants, replicated in 2,795 participants. The results indicate that <1% of variance in plasma cortisol is accounted for by genetic variation in a single region of chromosome 14. This locus spans SERPINA6, encoding corticosteroid binding globulin (CBG, the major cortisol-binding protein in plasma), and SERPINA1, encoding alpha 1-antitrypsin (which inhibits cleavage of the reactive centre loop that releases cortisol from CBG). Three partially independent signals were identified within the region, represented by common SNPs; detailed biochemical investigation in a nested sub-cohort showed all these SNPs were associated with variation in total cortisol binding activity in plasma, but some variants influenced total CBG concentrations while the top hit (rs12589136) influenced the immunoreactivity of the reactive centre loop of CBG. Exome chip and 1000 Genomes imputation analysis of this locus in the CROATIA-Korcula cohort identified missense mutations in SERPINA6 and SERPINA1 that did not account for the effects of common variants. These findings reveal a novel common genetic source of variation in binding of cortisol by CBG, and reinforce the key role of CBG in determining plasma cortisol levels. In turn this genetic variation may contribute to cortisol-associated degenerative diseases.

  • 14. Bonamy, Anna-Karin Edstedt
    et al.
    Parikh, Nisha I
    Cnattingius, Sven
    Ludvigsson, Jonas F
    Ingelsson, Erik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
    Birth characteristics and subsequent risks of maternal cardiovascular disease: effects of gestational age and fetal growth2011In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 124, no 25, p. 2839-2846Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Prior studies showing an inverse relationship between low birth weight in offspring and maternal risks of cardiovascular diseases (CVD) are limited by lack of information on gestational age and/or insufficient adjustment for confounders.

    METHODS AND RESULTS: In a nationwide Swedish study, we included information on 923 686 women and their first singleton births between 1983 and 2005. Cox proportional hazards models were used to study associations between gestational length, fetal growth, and maternal incident hospitalization or death from CVD (coronary heart disease, cerebrovascular events, and heart failure). Multivariable adjusted models accounted for birth year, income, education, country of birth, smoking, diabetes mellitus, hypertension, and preeclampsia. The risk of maternal CVD increased with decreasing gestational age whereas the risk increase related to fetal growth appeared to be restricted to very small-for-gestational-age (SGA) infants. Compared with mothers of non-SGA infants born at term, the hazard ratio of CVD ranged from 1.39 (95% confidence interval 1.22-1.58) to 2.57 (95% confidence interval 1.97-3.34) among mothers to moderately and very preterm infants, respectively. There was a significant interaction between preterm birth and fetal growth with respect to mothers' risk of CVD (P<0.001). Among mothers to very SGA infants, the hazard ratio of CVD ranged from 1.38 (95% confidence interval 1.15-1.65) to 3.40 (95% confidence interval 2.26-5.11) in mothers to term and very preterm infants, respectively.

    CONCLUSIONS: Delivery of a preterm or SGA infant is associated with later life maternal hospitalization or death from CVD even after accounting for socioeconomic factors, smoking, and pregnancy-related complications.

  • 15. Broeckling, Corey D.
    et al.
    Heuberger, Adam L.
    Prince, Jonathan A.
    Ingelsson, Erik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
    Prenni, Jessica E.
    Assigning precursor-product ion relationships in indiscriminant MS/MS data from non-targeted metabolite profiling studies2013In: Metabolomics, ISSN 1573-3882, E-ISSN 1573-3890, Vol. 9, no 1, p. 33-43Article in journal (Refereed)
    Abstract [en]

    Tandem mass spectrometry using precursor ion selection (MS/MS) is an invaluable tool for structural elucidation of small molecules. In non-targeted metabolite profiling studies, instrument duty cycle limitations and experimental costs have driven efforts towards alternate approaches. Recently, researchers have begun to explore methods for collecting indiscriminant MS/MS (idMS/MS) data in which the fragmentation process does not involve precursor ion isolation. While this approach has many advantages, importantly speed, sensitivity and coverage, confident assignment of precursor-product ion relationships is challenging, which has inhibited broad adoption of the technique. Here, we present an approach that uses open source software to improve the assignment of precursor-product relationships in idMS/MS data by appending a dataset-wide correlational analysis to existing tools. The utility of the approach was demonstrated using a dataset of standard compounds spiked into a malt-barley background, as well as unspiked human serum. The workflow was able to recreate idMS/MS spectra which are highly similar to standard MS/MS spectra of authentic standards, even in the presence of a complex matrix background. The application of this approach has the potential to generate high quality idMS/MS spectra for each detectable molecular feature, which will streamline the identification process for non-targeted metabolite profiling studies.

  • 16.
    Burgess, Stephen
    et al.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cardiovasc Epidemiol Unit, Cambridge, England..
    Bowden, Jack
    Univ Bristol, Sch Social & Community Med, Med Res Council, Integrat Epidemiol Unit, Bristol, Avon, England..
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Thompson, Simon G.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cardiovasc Epidemiol Unit, Cambridge, England..
    Sensitivity Analyses for Robust Causal Inference from Mendelian Randomization Analyses with Multiple Genetic Variants2017In: Epidemiology, ISSN 1044-3983, E-ISSN 1531-5487, Vol. 28, no 1, p. 30-42Article, review/survey (Refereed)
    Abstract [en]

    Mendelian randomization investigations are becoming more powerful and simpler to perform, due to the increasing size and coverage of genome-wide association studies and the increasing availability of summarized data on genetic associations with risk factors and disease outcomes. However, when using multiple genetic variants from different gene regions in a Mendelian randomization analysis, it is highly implausible that all the genetic variants satisfy the instrumental variable assumptions. This means that a simple instrumental variable analysis alone should not be relied on to give a causal conclusion. In this article, we discuss a range of sensitivity analyses that will either support or question the validity of causal inference from a Mendelian randomization analysis with multiple genetic variants. We focus on sensitivity analyses of greatest practical relevance for ensuring robust causal inferences, and those that can be undertaken using summarized data. Aside from cases in which the justification of the instrumental variable assumptions is supported by strong biological understanding, a Mendelian randomization analysis in which no assessment of the robustness of the findings to violations of the instrumental variable assumptions has been made should be viewed as speculative and incomplete. In particular, Mendelian randomization investigations with large numbers of genetic variants without such sensitivity analyses should be treated with skepticism.

  • 17. Bäck, Magnus
    et al.
    Yin, Li
    Nagy, Edit
    Ingelsson, Erik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
    The leukotriene receptor antagonist montelukast and aortic stenosis2013In: British Journal of Clinical Pharmacology, ISSN 0306-5251, E-ISSN 1365-2125, Vol. 75, no 1, p. 280-281Article in journal (Refereed)
  • 18.
    Campbell, William
    et al.
    Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA..
    Ganna, Andrea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Swedden..
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Janssens, A. Cecile J. W.
    Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA.;Vrije Univ Amsterdam Med Ctr, EMGO Inst Hlth & Care Res, Sect Community Genet, Dept Clin Genet, NL-1007 MB Amsterdam, Netherlands..
    Prediction impact curve is a new measure integrating intervention effects in the evaluation of risk models2016In: Journal of Clinical Epidemiology, ISSN 0895-4356, E-ISSN 1878-5921, Vol. 69, p. 89-95Article in journal (Refereed)
    Abstract [en]

    Objective: We propose a new measure of assessing the performance of risk models, the area under the prediction impact curve (auPIC), which quantifies the performance of risk models in terms of their average health impact in the population. Study Design and Setting: Using simulated data, we explain how the prediction impact curve (PIC) estimates the percentage of events prevented when a risk model is used to assign high-risk individuals to an intervention. We apply the PIC to the Atherosclerosis Risk in Communities (ARIC) Study to illustrate its application toward prevention of coronary heart disease. Results: We estimated that if the ARIC cohort received statins at baseline, 5% of events would be prevented when the risk model was evaluated at a cutoff threshold of 20% predicted risk compared to 1% when individuals were assigned to the intervention without the use of a model. By calculating the auPIC, we estimated that an average of 15% of events would be prevented when considering performance across the entire interval. Conclusion: We conclude that the PIC is a clinically meaningful measure for quantifying the expected health impact of risk models that supplements existing measures of model performance.

  • 19.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Carrero, Juan Jesus
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Feldreich, Tobias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Stenemo, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Use of Proteomics To Investigate Kidney Function Decline over 5 Years2017In: American Society of Nephrology. Clinical Journal, ISSN 1555-9041, E-ISSN 1555-905X, Vol. 12, no 8, p. 1226-1235Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND OBJECTIVES: Using a discovery/replication approach, we investigated associations between a multiplex panel of 80 circulating proteins associated with cardiovascular pathology or inflammation, and eGFR decline per year and CKD incidence.

    DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used two cohorts, the Prospective Investigation of the Vasculature in Uppsala Seniors Study (PIVUS; n=687, mean age of 70 years, 51% women) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n=360 men, mean age of 78 years), with 5-year follow-up data on eGFR. There were 231 and 206 incident cases of CKD during follow-up in the PIVUS and ULSAM studies, respectively. Proteomic profiling of 80 proteins was assessed by a multiplex assay (proximity extension assay). The assay uses two antibodies for each protein and a PCR step to achieve a high-specific binding and the possibility to measure multiple proteins in parallel, but gives no absolute concentrations.

    RESULTS: In the discovery cohort from the PIVUS Study, 28 plasma proteins were significantly associated with eGFR decline per year, taking into account the multiple testing. Twenty of these proteins were significantly associated with eGFR decline per year in the replication cohort from the ULSAM Study after adjustment for age, sex, cardiovascular risk factors, medications, and urinary albumin-to-creatinine ratio (in order of significance: TNF-related apoptosis-inducing ligand receptor 2*, CD40L receptor, TNF receptor 1*, placenta growth factor*, thrombomodulin*, urokinase plasminogen activator surface receptor*, growth/differentiation factor 15*, macrophage colony-stimulating factor 1, fatty acid-binding protein*, cathepsin D, resistin, kallikrein 11*, C-C motif chemokine 3, proteinase-activated receptor 1*, cathepsin L, chitinase 3-like protein 1, TNF receptor 2*, fibroblast growth factor 23*, monocyte chemotactic protein 1, and kallikrein 6). Moreover, 11 of the proteins predicted CKD incidence (marked with * above). No protein consistently predicted eGFR decline per year independently of baseline eGFR in both cohorts.

    CONCLUSIONS: Several circulating proteins involved in phosphate homeostasis, inflammation, apoptosis, extracellular matrix remodeling, angiogenesis, and endothelial dysfunction were associated with worsening kidney function. Multiplex proteomics appears to be a promising way of discovering novel aspects of kidney disease pathology.

  • 20.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Juhlin, C Christofer
    Larsson, Tobias E
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Soluble tumor necrosis factor receptor 1 (sTNFR1) is associated with increased total mortality due to cancer and cardiovascular causes: Findings from two community based cohorts of elderly2014In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 237, no 1, p. 236-242Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Experimental evidence support soluble receptors for tumor necrosis factor alpha as important mediators of the underlying pathology leading to cardiovascular disease and cancer. However, prospective data concerning the relation between circulating soluble tumor necrosis factor receptor-1 (sTNFR1) and mortality in humans are lacking. We aimed to explore and validate the association between sTNFR1 and mortality, and to explore the influence of other established risk factors for mortality, including other inflammatory markers.

    METHODS: The association between serum sTNFR1and the risk for mortality was investigated in two community-based cohorts of elderly: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 50%, n = 1005, mean age 70 years, median follow-up 7.9 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 775, mean age 77 years, median follow-up 8.1 years).

    RESULTS: In total, 101 participants in PIVUS and 274 in ULSAM died during follow-up. In multivariable Cox regression models adjusted for inflammation, lifestyle and established cardiovascular risk factors, one standard deviation (SD) higher sTNFR1 was associated with a hazard ratio (HR) for mortality of 1.37, 95% confidence interval (CI) 1.17-1.60, in PIVUS and HR 1.22, 95% CI 1.10-1.37 in ULSAM. Moreover, circulatingsTNFR1 was associated with cardiovascular mortality (HR per SD of sTNFR1, 1.24, 95% CI 1.07-1.44) and cancer mortality (HR per SD of sTNFR1, 1.32, 95% CI 1.11-1.57) in the ULSAM cohort. High levels of sTNFR1 identified individuals with increased risk of mortality among those with high as well as low levels of systemic inflammation.

    CONCLUSIONS: An association between circulating sTNFR1 and an increased risk for mortality was found and validated in two independent community-based cohorts. The future clinical role of sTNFR1 to identify high risk patients for adverse outcomes and mortality has yet to be determined.

  • 21.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Helmersson-Karlqvist, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Larsson, Tobias E
    Bottai, Matteo
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Urinary Kidney Injury Molecule-1 and the Risk of Cardiovascular Mortality in Elderly Men2014In: Clinical journal of the American Society of Nephrology : CJASN, ISSN 1555-905X, Vol. 9, no 8, p. 1393-1401Article in journal (Refereed)
    Abstract [en]

    Background and objectives

    Kidney injury molecule-1 (KIM-1) has been suggested as a clinically relevant highly specific biomarker of acute kidney tubular damage. However, community-based data on the association between urinary levels of KIM-1 and the risk for cardiovascular mortality are lacking. This study aimed to investigate the association between urinary KIM-1 and cardiovascular mortality.

    Design, setting, participants, & measurements

    This was a prospective study, using the community-based Uppsala Longitudinal Study of Adult Men (N=590; mean age 77 years; baseline period, 1997–2001; median follow-up 8.1 years; end of follow-up, 2008).

    Results

    During follow-up, 89 participants died of cardiovascular causes (incidence rate, 2.07 per 100 person-years at risk). Models were adjusted for cardiovascular risk factors (age, systolic BP, diabetes, smoking, body mass index, total cholesterol, HDL cholesterol, antihypertensive treatment, lipid-lowering treatment, aspirin treatment, and history of cardiovascular disease) and for markers of kidney dysfunction and damage (cystatin C–based eGFR and urinary albumin/creatinine ratio). Higher urinary KIM-1/creatinine (from 24-hour urine collections) was associated with a higher risk for cardiovascular mortality (hazard ratio per SD increase, 1.27; 95% confidence interval [95% CI], 1.05 to 1.54; P=0.01). Participants with a combination of high KIM-1/creatinine (upper quintile, ≥175 ng/mmol), low eGFR (≤60 ml/min per 1.73 m2), and microalbuminuria/macroalbuminuria (albumin/creatinine ratio≥3 g/mol) had a >8-fold increased risk compared with participants with low KIM-1/creatinine (<175 ng/mmol), normal eGFR (>60 ml/min per 1.73 m2), and normoalbuminuria (albumin/creatinine ratio<3 g/mol) (hazard ratio, 8.56; 95% CI, 4.17 to 17.56; P<0.001).

    Conclusions

    These findings suggest that higher urinary KIM-1 may predispose to a higher risk of cardiovascular mortality independently of established cardiovascular risk factors, eGFR, and albuminuria. Additional studies are needed to further assess the utility of measuring KIM-1 in the clinical setting.

  • 22.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ruge, Toralph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Association between circulating endostatin, hypertension duration, and hypertensive target-organ damage2013In: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 62, no 6, p. 1146-1151Article in journal (Refereed)
    Abstract [en]

    Our aim is to study associations between circulating endostatin, hypertension duration, and hypertensive target-organ damage. Long-term hypertension induces cardiovascular and renal remodeling. Circulating endostatin, a biologically active derivate of collagen XVIII, has been suggested to be a relevant marker for extracellular matrix turnover and remodeling in various diseases. However, the role of endostatin in hypertension and hypertensive target-organ damage is unclear. Serum endostatin was measured in 2 independent community-based cohorts: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 51%; n=812; mean age, 75 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n=785; mean age, 77.6 years). Retrospective data on blood pressure measurements and antihypertensive medication (PIVUS >5 years, ULSAM >27 years), and cross-sectional data on echocardiographic left ventricular mass, endothelial function (endothelium-dependent vasodilation assessed by the invasive forearm model), and urinary albumin/creatinine ratio were available. In PIVUS, participants with ≥5 years of history of hypertension portrayed 0.42 SD (95% confidence interval, 0.23-0.61; P<0.001) higher serum endostatin, compared with that of normotensives. This association was replicated in ULSAM, in which participants with 27 years hypertension duration had the highest endostatin (0.57 SD higher; 95% confidence interval, 0.35-0.80; P<0.001). In addition, higher endostatin was associated with higher left ventricular mass, worsened endothelial function, and higher urinary albumin/creatinine ratio (P<0.03 for all) in participants with prevalent hypertension. Circulating endostatin is associated with the duration of hypertension, and vascular, myocardial, and renal indices of hypertensive target-organ damage. Further studies are warranted to assess the prognostic role of endostatin in individuals with hypertension.

  • 23.
    Choi, Seung Hoan
    et al.
    Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.;Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.;Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA..
    Ruggiero, Daniela
    CNR, Inst Genet & Biophys, Naples, Italy..
    Sorice, Rossella
    CNR, Inst Genet & Biophys, Naples, Italy..
    Song, Ci
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Natl Heart Lung & Blood Inst Framingham Heart Stu, Populat Sci Branch, Framingham, MA USA.;Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Nutile, Teresa
    CNR, Inst Genet & Biophys, Naples, Italy..
    Smith, Albert Vernon
    Iceland Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Reykjavik, Iceland..
    Concas, Maria Pina
    CNR, Inst Populat Genet, Sassari, Italy..
    Traglia, Michela
    Ist Sci San Raffaele, Div Genet & Cell Biol, I-20132 Milan, Italy..
    Barbieri, Caterina
    Ist Sci San Raffaele, Div Genet & Cell Biol, I-20132 Milan, Italy..
    Ndiaye, Ndeye Coumba
    Univ Lorraine, Fac Pharm, UMR INSERM U1122, IGE PCV Interact Gene Environm Physiopathol Cardi, Nancy, France..
    Stathopoulou, Maria G.
    Univ Lorraine, Fac Pharm, UMR INSERM U1122, IGE PCV Interact Gene Environm Physiopathol Cardi, Nancy, France..
    Lagou, Vasiliki
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Maestrale, Giovanni Battista
    CNR, Inst Populat Genet, Sassari, Italy..
    Sala, Cinzia
    Ist Sci San Raffaele, Div Genet & Cell Biol, I-20132 Milan, Italy..
    Debette, Stephanie
    Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.;Bordeaux Univ Hosp, Dept Neurol, Bordeaux, France.;INSERM, U897, Bordeaux, France..
    Kovacs, Peter
    Univ Leipzig, IFB Adipos Dis, D-04109 Leipzig, Germany..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lamont, John
    Randox Labs, Crumlin, Ireland..
    Fitzgerald, Peter
    Randox Labs, Crumlin, Ireland..
    Toenjes, Anke
    Univ Leipzig, Dept Med, D-04109 Leipzig, Germany..
    Gudnason, Vilmundur
    Iceland Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Reykjavik, Iceland..
    Toniolo, Daniela
    Ist Sci San Raffaele, Div Genet & Cell Biol, I-20132 Milan, Italy..
    Pirastu, Mario
    CNR, Inst Populat Genet, Sassari, Italy..
    Bellenguez, Celine
    Inst Pasteur, F-59019 Lille, France.;INSEM, U744, Lille, France.;Univ Lille Nord France, Lille, France..
    Vasan, Ramachandran S.
    Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA.;Boston Univ, Sch Med, Dept Med, Sect Prevent Med & Epidemiol, Boston, MA 02215 USA.;Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA..
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Leutenegger, Anne-Louise
    INSERM, U946, Paris, France.;Univ Paris Diderot, Sorbonne Paris Cite, IUH, UMR S 946, Paris, France..
    Johnson, Andrew D.
    Natl Heart Lung & Blood Inst Framingham Heart Stu, Populat Sci Branch, Framingham, MA USA..
    DeStefano, Anita L.
    Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.;Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.;Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA..
    Visvikis-Siest, Sophie
    Univ Lorraine, Fac Pharm, UMR INSERM U1122, IGE PCV Interact Gene Environm Physiopathol Cardi, Nancy, France..
    Seshadri, Sudha
    Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.;Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA..
    Ciullo, Marina
    CNR, Inst Genet & Biophys, Naples, Italy..
    Six Novel Loci Associated with Circulating VEGF Levels Identified by a Meta-analysis of Genome-Wide Association Studies2016In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 12, no 2, article id e1005874Article in journal (Refereed)
    Abstract [en]

    Vascular endothelial growth factor (VEGF) is an angiogenic and neurotrophic factor, secreted by endothelial cells, known to impact various physiological and disease processes from cancer to cardiovascular disease and to be pharmacologically modifiable. We sought to identify novel loci associated with circulating VEGF levels through a genome-wide association meta-analysis combining data from European-ancestry individuals and using a dense variant map from 1000 genomes imputation panel. Six discovery cohorts including 13,312 samples were analyzed, followed by in-silico and de-novo replication studies including an additional 2,800 individuals. A total of 10 genome-wide significant variants were identified at 7 loci. Four were novel loci (5q14.3, 10q21.3, 16q24.2 and 18q22.3) and the leading variants at these loci were rs114694170 (MEF2C, P = 6.79x10(-13)), rs74506613 (JMJD1C, P = 1.17x10(-19)), rs4782371 (ZFPM1, P = 1.59x10(-9)) and rs2639990 (ZADH2, P = 1.72x10(-8)), respectively. We also identified two new independent variants (rs34528081, VEGFA, P = 1.52x10(-18); rs7043199, VLDLR-AS1, P = 5.12x10(-14)) at the 3 previously identified loci and strengthened the evidence for the four previously identified SNPs (rs6921438, LOC100132354, P = 7.39x10(-1467); rs1740073, C6orf223, P = 2.34x10(-17); rs6993770, ZFPM2, P = 2.44x10(-60); rs2375981, KCNV2, P = 1.48x10(-100)). These variants collectively explained up to 52% of the VEGF phenotypic variance. We explored biological links between genes in the associated loci using Ingenuity Pathway Analysis that emphasized their roles in embryonic development and function. Gene set enrichment analysis identified the ERK5 pathway as enriched in genes containing VEGF associated variants. eQTL analysis showed, in three of the identified regions, variants acting as both cis and trans eQTLs for multiple genes. Most of these genes, as well as some of those in the associated loci, were involved in platelet biogenesis and functionality, suggesting the importance of this process in regulation of VEGF levels. This work also provided new insights into the involvement of genes implicated in various angiogenesis related pathologies in determining circulating VEGF levels. The understanding of the molecular mechanisms by which the identified genes affect circulating VEGF levels could be important in the development of novel VEGF-related therapies for such diseases.

  • 24.
    Christophersen, Ingrid E.
    et al.
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Vestre Viken Hosp Trust, Baerum Hosp, Dept Med Res, Rud, Norway..
    Rienstra, Michiel
    Univ Groningen, Dept Cardiol, Univ Med Ctr Groningen, Groningen, Netherlands..
    Roselli, Carolina
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, Neuherberg, Germany.;Ludwig Maximilians Univ Munchen, Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany..
    Yin, Xiaoyan
    NHLBI, Framingham, MA USA.;Boston Univ Framingham Heart Study, Framingham, MA USA.;Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA..
    Geelhoed, Bastiaan
    Univ Groningen, Dept Cardiol, Univ Med Ctr Groningen, Groningen, Netherlands..
    Barnard, John
    Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA.;Cleveland Clin, Dept Cellular & Mol Med, Cleveland, OH 44106 USA.;Cleveland Clin, Dept Mol Cardiol, Cleveland, OH 44106 USA.;Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA..
    Lin, Honghuang
    NHLBI, Framingham, MA USA.;Boston Univ Framingham Heart Study, Framingham, MA USA.;Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA..
    Arking, Dan E.
    Johns Hopkins Univ Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA..
    Smith, Albert V.
    Iceland Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Albert, Christine M.
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA.;Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA..
    Chaffin, Mark
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA..
    Tucker, Nathan R.
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA..
    Li, Molong
    Klarin, Derek
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA..
    Bihlmeyer, Nathan A.
    Johns Hopkins Univ Sch Med, McKusick Nathans Inst Genet Med, Predoctoral Training Program Human Genet, Baltimore, MD USA..
    Low, Siew-Kee
    RIKEN, Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, Japan..
    Weeke, Peter E.
    Vanderbilt Univ, Med Ctr, Dept Med, 221 Kirkland Hall, Nashville, TN 37235 USA.;Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, Heart Ctr, Copenhagen, Denmark..
    Mueller-Nurasyid, Martina
    Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, Neuherberg, Germany.;Univ Hosp Munich, Ludwig Maximilians Univ, Dept Med 1, Munich, Germany.;DZHK German Ctr Cardiovasc Res, Munich Heart Alliance, Munich, Germany..
    Smith, J. Gustav
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Lund Univ, Clin Sci, Molecular Epidemiol & Cardiol, Lund, Sweden..
    Brody, Jennifer A.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA..
    Niemeijer, Maartje N.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Doerr, Marcus
    Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany.;DZHK German Ctr Cardiovasc Res, Greifswald, Germany..
    Trompet, Stella
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands..
    Huffman, Jennifer
    Univ Edinburgh, Inst Genet & Mol Med, MRC, Human Genet Unit, Edinburgh, Midlothian, Scotland..
    Gustafsson, Stefan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Schurmann, Claudia
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA..
    Kleber, Marcus E.
    Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Heidelberg, Germany..
    Lyytikainen, Leo-Pekka
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Sch Med, Tampere, Finland..
    Seppala, Ilkka
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Sch Med, Tampere, Finland..
    Malik, Rainer
    Klinikum Univ Munchen, Inst Stroke & Dementia Res, Ludwig Maximilians Univ, Munich, Germany..
    Horimoto, Andrea R. V. R.
    Univ Sao Paulo, Heart Inst, Lab Genet & Mol Cardiol, Sao Paulo, Brazil..
    Perez, Marco
    Stanford Univ, Dept Cardiovasc Med, Stanford, CA 94305 USA..
    Sinisalo, Juha
    Univ Helsinki, Cent Hosp, Heart & Lung Ctr HUS, Helsinki, Finland..
    Aeschbacher, Stefanie
    Univ Basel Hosp, Dept Med, Basel, Switzerland.;Cardiovasc Res Inst Basel, Basel, Switzerland..
    Theriault, Sebastien
    Populat Hlth Res Inst, Hamilton, ON, Canada.;McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada..
    Yao, Jie
    Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA..
    Radmanesh, Farid
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA..
    Weiss, Stefan
    DZHK German Ctr Cardiovasc Res, Greifswald, Germany.;Univ Med, Interfac Inst Genet & Funct Gen, Greifswald, Germany.;Ernst Moritz Arndt Univ Greifswald, Greifswald, Germany..
    Teumer, Alexander
    DZHK German Ctr Cardiovasc Res, Greifswald, Germany.;Univ Med Greifswald, Inst Community Med, Greifswald, Germany..
    Choi, Seung Hoan
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA..
    Weng, Lu-Chen
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA..
    Clauss, Sebastian
    Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Univ Hosp Munich, Ludwig Maximilians Univ, Dept Med 1, Munich, Germany.;DZHK German Ctr Cardiovasc Res, Munich Heart Alliance, Munich, Germany..
    Deo, Rajat
    Univ Penn, Perelman Sch Med, Dept Med, Div Cardiovasc Med, Philadelphia, PA 19104 USA..
    Rader, Daniel J.
    Univ Penn, Perelman Sch Med, Dept Med, Div Cardiovasc Med, Philadelphia, PA 19104 USA..
    Shah, Svati H.
    Duke Univ, Sch Med, Dept Med, Div Cardiol, Durham, NC 27706 USA..
    Sun, Albert
    Duke Univ, Sch Med, Dept Med, Div Cardiol, Durham, NC 27706 USA..
    Hopewell, Jemma C.
    Univ Oxford, CTSU Nuffield Dept Populat Hlth, Oxford, England..
    Debette, Stephanie
    Bordeaux Populat Hlth Ctr, INSERM U1219, Bordeaux, France.;Univ Bordeaux, Bordeaux, France.;Bordeaux Univ Hosp, Dept Neurol, Bordeaux, France.;Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA..
    Chauhan, Ganesh
    Bordeaux Populat Hlth Ctr, INSERM U1219, Bordeaux, France.;Univ Bordeaux, Bordeaux, France..
    Yang, Qiong
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA..
    Worrall, Bradford B.
    Univ Virginia Hlth Syst, Dept Neurol, Charlottesville, VA USA.;Univ Virginia Hlth Syst, Dept Publ Hlth Sci, Charlottesville, VA USA..
    Pare, Guillaume
    Populat Hlth Res Inst, Hamilton, ON, Canada.;McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada..
    Kamatani, Yoichiro
    RIKEN, Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, Japan..
    Hagemeijer, Yanick P.
    Univ Groningen, Dept Cardiol, Univ Med Ctr Groningen, Groningen, Netherlands..
    Verweij, Niek
    Univ Groningen, Dept Cardiol, Univ Med Ctr Groningen, Groningen, Netherlands..
    Siland, Joylene E.
    Univ Groningen, Dept Cardiol, Univ Med Ctr Groningen, Groningen, Netherlands..
    Kubo, Michiaki
    RIKEN, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan..
    Smith, Jonathan D.
    Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA.;Cleveland Clin, Dept Cellular & Mol Med, Cleveland, OH 44106 USA.;Cleveland Clin, Dept Mol Cardiol, Cleveland, OH 44106 USA.;Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA..
    Van Wagoner, David R.
    Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA.;Cleveland Clin, Dept Cellular & Mol Med, Cleveland, OH 44106 USA.;Cleveland Clin, Dept Mol Cardiol, Cleveland, OH 44106 USA.;Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA..
    Bis, Joshua C.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA..
    Perz, Siegfried
    Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Epidemiol 2, Neuherberg, Germany..
    Psaty, Bruce M.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.;Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.;Univ Washington, Cardiovasc Hlth Res Unit, Washington, DC USA.;Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.;Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA..
    Ridker, Paul M.
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA.;Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA..
    Magnani, Jared W.
    NHLBI, Framingham, MA USA.;Boston Univ Framingham Heart Study, Framingham, MA USA.;Boston Univ, Sch Med, Dept Med, Boston, MA 02215 USA..
    Harris, Tamara B.
    Natl Inst Aging, Lab Epidemiol Demog & Biometry, Bethesda, MD USA..
    Launer, Lenore J.
    Natl Inst Aging, Lab Epidemiol Demog & Biometry, Bethesda, MD USA..
    Shoemaker, M. Benjamin
    Vanderbilt Univ, Med Ctr, Dept Med, 221 Kirkland Hall, Nashville, TN 37235 USA..
    Padmanabhan, Sandosh
    Univ Glasgow, BHF Glasgow Cardiovasc Res Ctr, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland..
    Haessler, Jeffrey
    Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA..
    Bartz, Traci M.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.;Univ Washington, Dept Biostat, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA..
    Waldenberger, Melanie
    DZHK German Ctr Cardiovasc Res, Munich Heart Alliance, Munich, Germany.;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Epidemiol 2, Neuherberg, Germany.;Helmholtz Zentrum Munchen German Res Ctr Environm, Res Unit Mol Epidemiol, Neuherberg, Germany..
    Lichtner, Peter
    Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Human Genet, Neuherberg, Germany..
    Arendt, Marina
    Univ Hosp Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany..
    Krieger, Jose E.
    Univ Sao Paulo, Heart Inst, Lab Genet & Mol Cardiol, Sao Paulo, Brazil..
    Kahonen, Mika
    Univ Tampere, Sch Med, Tampere, Finland.;Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland..
    Risch, Lorenz
    Univ Bern, Univ Inst Clin Chem, Bern, Switzerland.;Labormed Zentrum Dr Risch, Schaan, Liechtenstein..
    Mansur, Alfredo J.
    Univ Sao Paulo, Heart Inst, Sao Paulo, Brazil..
    Peters, Annette
    DZHK German Ctr Cardiovasc Res, Munich Heart Alliance, Munich, Germany.;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Epidemiol 2, Neuherberg, Germany.;German Ctr Diabet Res, Neuherberg, Germany..
    Smith, Blair H.
    Univ Dundee, Div Populat Hlth Sci, Dundee, Scotland..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Scott, Stuart A.
    Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA..
    Lu, Yingchang
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA..
    Bottinger, Erwin B.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA..
    Hernesniemi, Jussi
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Sch Med, Tampere, Finland.;Tampere Univ Hosp, Heart Hosp, Dept Cardiol, Tampere, Finland..
    Lindgren, Cecilia M.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Wong, Jorge A.
    McMaster Univ, Div Cardiol Hamilton Hlth Sci, Hamilton, ON, Canada..
    Huang, Jie
    Boston VA Res Inst Inc, Boston, MA USA..
    Eskola, Markku
    Univ Tampere, Sch Med, Tampere, Finland.;Tampere Univ Hosp, Heart Hosp, Dept Cardiol, Tampere, Finland..
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England..
    Ford, Ian
    Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland..
    Reiner, Alex P.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.;Univ Glasgow, BHF Glasgow Cardiovasc Res Ctr, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland..
    Delgado, Graciela
    Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Heidelberg, Germany..
    Chen, Lin Y.
    Univ Minnesota, Dept Med, Med Sch, Cardiovasc Div, Box 736 UMHC, Minneapolis, MN 55455 USA..
    Chen, Yii-Der Ida
    Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA..
    Sandhu, Roopinder K.
    Univ Alberta, Div Cardiol, Edmonton, AB, Canada..
    Li, Man
    Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.;Univ Utah, Sch Med, Div Nephrol & Hypertens, Internal Med, Salt Lake City, UT USA..
    Boerwinkle, Eric
    Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA..
    Eisele, Lewin
    Univ Hosp Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany..
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Rost, Natalia
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Acute Stroke Serv, Boston, MA 02114 USA..
    Anderson, Christopher D.
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA..
    Taylor, Kent D.
    Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA..
    Campbell, Archie
    Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Generat Scotland, Edinburgh, Midlothian, Scotland..
    Magnusson, Patrik K.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Porteous, David
    Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Generat Scotland, Edinburgh, Midlothian, Scotland..
    Hocking, Lynne J.
    Univ Aberdeen, Div Appl Med, Musculoskeletal Res Programme, Aberdeen, Scotland..
    Vlachopoulou, Efthymia
    Univ Helsinki, Medicum, Transplantat Lab, Helsinki, Finland..
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Nikus, Kjell
    Univ Tampere, Sch Med, Tampere, Finland.;Tampere Univ Hosp, Heart Hosp, Dept Cardiol, Tampere, Finland..
    Orho-Melander, Marju
    Lund Univ, Dept Clin Sci, Malmo, Sweden..
    Hamsten, Anders
    Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Cardiovasc Genet & Genom Grp, Stockholm, Sweden..
    Heeringa, Jan
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Denny, Joshua C.
    Vanderbilt Univ, Med Ctr, Dept Med, 221 Kirkland Hall, Nashville, TN 37235 USA..
    Kriebel, Jennifer
    Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Epidemiol 2, Neuherberg, Germany.;Helmholtz Zentrum Munchen German Res Ctr Environm, Res Unit Mol Epidemiol, Neuherberg, Germany.;German Ctr Diabet Res, Neuherberg, Germany..
    Darbar, Dawood
    Univ Illinois, Dept Med & Pharmacol, Chicago, IL USA..
    Newton-Cheh, Christopher
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA..
    Shaffer, Christian
    Vanderbilt Univ, Med Ctr, Dept Med, 221 Kirkland Hall, Nashville, TN 37235 USA..
    Macfarlane, Peter W.
    Univ Glasgow, Coll Med Vet & Sci, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland..
    Heilmann-Heimbach, Stefanie
    Univ Bonn, Inst Human Genet, Bonn, Germany.;Univ Bonn, Life & Brain Res Ctr, Dept Gen, Bonn, Germany..
    Almgren, Peter
    Lund Univ, Dept Clin Sci, Malmo, Sweden..
    Huang, Paul L.
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA..
    Sotoodehnia, Nona
    Univ Washington, Cardiovasc Hlth Res Unit, Washington, DC USA..
    Soliman, Elsayed Z.
    Wake Forest Sch Med, Epidemiol Cardiol Res Ctr EPICARE, Winston Salem, NC USA..
    Uitterlinden, Andre G.
    Erasmus MC, Dept Epidemiol & Internal Med, Rotterdam, Netherlands..
    Hofman, Albert
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Franco, Oscar H.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Voelker, Uwe
    DZHK German Ctr Cardiovasc Res, Greifswald, Germany.;Univ Med, Interfac Inst Genet & Funct Gen, Greifswald, Germany.;Ernst Moritz Arndt Univ Greifswald, Greifswald, Germany..
    Joeckel, Karl-Heinz
    Univ Hosp Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany..
    Sinner, Moritz F.
    Univ Hosp Munich, Ludwig Maximilians Univ, Dept Med 1, Munich, Germany.;DZHK German Ctr Cardiovasc Res, Munich Heart Alliance, Munich, Germany..
    Lin, Henry J.
    Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA..
    Guo, Xiuqing
    Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA..
    Dichgans, Martin
    Klinikum Univ Munchen, Inst Stroke & Dementia Res, Ludwig Maximilians Univ, Munich, Germany.;Munich Cluster Syst Neurol SyNergy, Munich, Germany.;German Ctr Neurodegenerat Dis DZNE, Munich, Germany..
    Ingelsson, Erik
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Kooperberg, Charles
    Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA..
    Melander, Olle
    Lund Univ, Clin Sci, Dept Internal Med, Malmo, Sweden..
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA..
    Laurikka, Jari
    Univ Tampere, Sch Med, Tampere, Finland.;Tampere Univ Hosp, Heart Hosp, Dept Cardio Thorac Surg, Tampere, Finland..
    Conen, David
    Univ Basel Hosp, Dept Med, Basel, Switzerland.;Cardiovasc Res Inst Basel, Basel, Switzerland..
    Rosand, Jonathan
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA..
    van der Harst, Pim
    Univ Groningen, Dept Cardiol, Univ Med Ctr Groningen, Groningen, Netherlands..
    Lokki, Marja-Liisa
    Univ Helsinki, Medicum, Transplantat Lab, Helsinki, Finland..
    Kathiresan, Sekar
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA..
    Pereira, Alexandre
    Univ Sao Paulo, Heart Inst, Lab Genet & Mol Cardiol, Sao Paulo, Brazil.;Harvard Med Sch, Dept Genet, Boston, MA USA..
    Jukema, J. Wouter
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands.;Durrer Ctr Cardiogenet Res, Amsterdam, Netherlands.;Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands..
    Hayward, Caroline
    Univ Edinburgh, Inst Genet & Mol Med, MRC, Human Genet Unit, Edinburgh, Midlothian, Scotland..
    Rotter, Jerome I.
    Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.;Harbor UCLA Med Ctr, LABioMed, Dept Med, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA..
    Maerz, Winfried
    Med Univ Graz, Inst Clin Med, Graz, Austria.;Med Univ Graz, Chem Lab Diagnost, Graz, Austria.;Synlab Holding Deutschland GmbH, Synlab Acad, Mannheim, Germany.;Synlab Holding Deutschland GmbH, Synlab Acad, Augsburg, Germany..
    Lehtimaki, Terho
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Sch Med, Tampere, Finland..
    Stricker, Bruno H.
    Erasmus MC, Dept Epidemiol & Internal Med, Rotterdam, Netherlands.;Inspectorate Hlth Care, Utrecht, Netherlands..
    Chung, Mina K.
    Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA.;Cleveland Clin, Dept Cellular & Mol Med, Cleveland, OH 44106 USA.;Cleveland Clin, Dept Mol Cardiol, Cleveland, OH 44106 USA.;Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA..
    Felix, Stephan B.
    Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany.;DZHK German Ctr Cardiovasc Res, Greifswald, Germany..
    Gudnason, Vilmundur
    Iceland Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Alonso, Alvaro
    Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA..
    Roden, Dan M.
    Vanderbilt Univ, Med Ctr, Dept Med, 221 Kirkland Hall, Nashville, TN 37235 USA..
    Kaeaeb, Stefan
    Univ Hosp Munich, Ludwig Maximilians Univ, Dept Med 1, Munich, Germany.;DZHK German Ctr Cardiovasc Res, Munich Heart Alliance, Munich, Germany..
    Chasman, Daniel I.
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA.;Brigham & Womens Hosp, Div Genet, 75 Francis St, Boston, MA 02115 USA..
    Heckbert, Susan R.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.;Univ Washington, Cardiovasc Hlth Res Unit, Washington, DC USA.;Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA..
    Benjamin, Emelia J.
    NHLBI, Framingham, MA USA.;Boston Univ Framingham Heart Study, Framingham, MA USA.;Boston Univ, Sch Med, Dept Med, Boston, MA 02215 USA.;Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA..
    Tanaka, Toshihiro
    RIKEN, Ctr Integrat Med Sci, Lab Cardiovasc Dis, Yokohama, Kanagawa, Japan.;Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Human Genet & Dis Divers, Tokyo, Japan..
    Lunetta, Kathryn L.
    NHLBI, Framingham, MA USA.;Boston Univ Framingham Heart Study, Framingham, MA USA..
    Lubitz, Steven A.
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA..
    Ellinor, Patrick T.
    Broad Inst & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA..
    Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation2017In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 49, no 6, p. 946-+Article in journal (Refereed)
    Abstract [en]

    Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death(1,2). Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups(3-7). To further define the genetic basis of atrial fibrillation, we performed large-scale, trans-ancestry meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 17,931 individuals with atrial fibrillation and 115,142 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,346 cases and 132,086 referents. We identified 12 new genetic loci that exceeded genome-wide significance, implicating genes involved in cardiac electrical and structural remodeling. Our results nearly double the number of known genetic loci for atrial fibrillation, provide insights into the molecular basis of atrial fibrillation, and may facilitate the identification of new potential targets for drug discovery(8).

  • 25. Chu, Audrey Y
    et al.
    Deng, Xuan
    Fisher, Virginia A
    Drong, Alexander
    Zhang, Yang
    Feitosa, Mary F
    Liu, Ching-Ti
    Weeks, Olivia
    Choh, Audrey C
    Duan, Qing
    Dyer, Thomas D
    Eicher, John D
    Guo, Xiuqing
    Heard-Costa, Nancy L
    Kacprowski, Tim
    Kent, Jack W
    Lange, Leslie A
    Liu, Xinggang
    Lohman, Kurt
    Lu, Lingyi
    Mahajan, Anubha
    O'Connell, Jeffrey R
    Parihar, Ankita
    Peralta, Juan M
    Smith, Albert V
    Zhang, Yi
    Homuth, Georg
    Kissebah, Ahmed H
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Laqua, René
    Launer, Lenore J
    Nauck, Matthias
    Olivier, Michael
    Peyser, Patricia A
    Terry, James G
    Wojczynski, Mary K
    Yao, Jie
    Bielak, Lawrence F
    Blangero, John
    Borecki, Ingrid B
    Bowden, Donald W
    Carr, John Jeffrey
    Czerwinski, Stefan A
    Ding, Jingzhong
    Friedrich, Nele
    Gudnason, Vilmunder
    Harris, Tamara B
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Johnson, Andrew D
    Kardia, Sharon L R
    Langefeld, Carl D
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Liu, Yongmei
    Mitchell, Braxton D
    Morris, Andrew P
    Mosley, Thomas H
    Rotter, Jerome I
    Shuldiner, Alan R
    Towne, Bradford
    Völzke, Henry
    Wallaschofski, Henri
    Wilson, James G
    Allison, Matthew
    Lindgren, Cecilia M
    Goessling, Wolfram
    Cupples, L Adrienne
    Steinhauser, Matthew L
    Fox, Caroline S
    Multiethnic genome-wide meta-analysis of ectopic fat depots identifies loci associated with adipocyte development and differentiation2017In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 49, no 1, p. 125-130Article in journal (Refereed)
    Abstract [en]

    Variation in body fat distribution contributes to the metabolic sequelae of obesity. The genetic determinants of body fat distribution are poorly understood. The goal of this study was to gain new insights into the underlying genetics of body fat distribution by conducting sample-size-weighted fixed-effects genome-wide association meta-analyses in up to 9,594 women and 8,738 men of European, African, Hispanic and Chinese ancestry, with and without sex stratification, for six traits associated with ectopic fat (hereinafter referred to as ectopic-fat traits). In total, we identified seven new loci associated with ectopic-fat traits (ATXN1, UBE2E2, EBF1, RREB1, GSDMB, GRAMD3 and ENSA; P < 5 × 10(-8); false discovery rate < 1%). Functional analysis of these genes showed that loss of function of either Atxn1 or Ube2e2 in primary mouse adipose progenitor cells impaired adipocyte differentiation, suggesting physiological roles for ATXN1 and UBE2E2 in adipogenesis. Future studies are necessary to further explore the mechanisms by which these genes affect adipocyte biology and how their perturbations contribute to systemic metabolic disease.

  • 26. Cornelis, M C
    et al.
    Byrne, E M
    Esko, T
    Nalls, M A
    Ganna, A
    Paynter, N
    Monda, K L
    Amin, N
    Fischer, K
    Renstrom, F
    Ngwa, J S
    Huikari, V
    Cavadino, A
    Nolte, I M
    Teumer, A
    Yu, K
    Marques-Vidal, P
    Rawal, R
    Manichaikul, A
    Wojczynski, M K
    Vink, J M
    Zhao, J H
    Burlutsky, G
    Lahti, J
    Mikkilä, V
    Lemaitre, R N
    Eriksson, J
    Musani, S K
    Tanaka, T
    Geller, F
    Luan, J
    Hui, J
    Mägi, R
    Dimitriou, M
    Garcia, M E
    Ho, W-K
    Wright, M J
    Rose, L M
    Magnusson, P K E
    Pedersen, N L
    Couper, D
    Oostra, B A
    Hofman, A
    Ikram, M A
    Tiemeier, H W
    Uitterlinden, A G
    van Rooij, F J A
    Barroso, I
    Johansson, I
    Xue, L
    Kaakinen, M
    Milani, L
    Power, C
    Snieder, H
    Stolk, R P
    Baumeister, S E
    Biffar, R
    Gu, F
    Bastardot, F
    Kutalik, Z
    Jacobs, D R
    Forouhi, N G
    Mihailov, E
    Lind, Lars
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lindgren, C
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Morris, A
    Jensen, M
    Khaw, K-T
    Luben, R N
    Wang, J J
    Männistö, S
    Perälä, M-M
    Kähönen, M
    Lehtimäki, T
    Viikari, J
    Mozaffarian, D
    Mukamal, K
    Psaty, B M
    Döring, A
    Heath, A C
    Montgomery, G W
    Dahmen, N
    Carithers, T
    Tucker, K L
    Ferrucci, L
    Boyd, H A
    Melbye, M
    Treur, J L
    Mellström, D
    Hottenga, J J
    Prokopenko, I
    Tönjes, A
    Deloukas, P
    Kanoni, S
    Lorentzon, M
    Houston, D K
    Liu, Y
    Danesh, J
    Rasheed, A
    Mason, M A
    Zonderman, A B
    Franke, L
    Kristal, B S
    Karjalainen, J
    Reed, D R
    Westra, H-J
    Evans, M K
    Saleheen, D
    Harris, T B
    Dedoussis, G
    Curhan, G
    Stumvoll, M
    Beilby, J
    Pasquale, L R
    Feenstra, B
    Bandinelli, S
    Ordovas, J M
    Chan, A T
    Peters, U
    Ohlsson, C
    Gieger, C
    Martin, N G
    Waldenberger, M
    Siscovick, D S
    Raitakari, O
    Eriksson, J G
    Mitchell, P
    Hunter, D J
    Kraft, P
    Rimm, E B
    Boomsma, D I
    Borecki, I B
    Loos, R J F
    Wareham, N J
    Vollenweider, P
    Caporaso, N
    Grabe, H J
    Neuhouser, M L
    Wolffenbuttel, B H R
    Hu, F B
    Hyppönen, E
    Järvelin, M-R
    Cupples, L A
    Franks, P W
    Ridker, P M
    van Duijn, C M
    Heiss, G
    Metspalu, A
    North, K E
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nettleton, J A
    van Dam, R M
    Chasman, D I
    Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption2015In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 20, no 5, p. 647-656Article in journal (Refereed)
    Abstract [en]

    Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to 91 462 coffee consumers of European ancestry with top single-nucleotide polymorphisms (SNPs) followed-up in ~30 062 and 7964 coffee consumers of European and African-American ancestry, respectively. Studies from both stages were combined in a trans-ethnic meta-analysis. Confirmed loci were examined for putative functional and biological relevance. Eight loci, including six novel loci, met GW significance (log10Bayes factor (BF)>5.64) with per-allele effect sizes of 0.03-0.14 cups per day. Six are located in or near genes potentially involved in pharmacokinetics (ABCG2, AHR, POR and CYP1A2) and pharmacodynamics (BDNF and SLC6A4) of caffeine. Two map to GCKR and MLXIPL genes related to metabolic traits but lacking known roles in coffee consumption. Enhancer and promoter histone marks populate the regions of many confirmed loci and several potential regulatory SNPs are highly correlated with the lead SNP of each. SNP alleles near GCKR, MLXIPL, BDNF and CYP1A2 that were associated with higher coffee consumption have previously been associated with smoking initiation, higher adiposity and fasting insulin and glucose but lower blood pressure and favorable lipid, inflammatory and liver enzyme profiles (P<5 × 10(-8)).Our genetic findings among European and African-American adults reinforce the role of caffeine in mediating habitual coffee consumption and may point to molecular mechanisms underlying inter-individual variability in pharmacological and health effects of coffee.

  • 27. Cornelis, Marilyn C
    et al.
    Kacprowski, Tim
    Menni, Cristina
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Pivin, Edward
    Adamski, Jerzy
    Artati, Anna
    Eap, Chin B
    Ehret, Georg
    Friedrich, Nele
    Ganna, Andrea
    Guessous, Idris
    Homuth, Georg
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Magnusson, Patrik K
    Mangino, Massimo
    Pedersen, Nancy L
    Pietzner, Maik
    Suhre, Karsten
    Völzke, Henry
    Bochud, Murielle
    Spector, Tim D
    Grabe, Hans J
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, USA..
    Genome-wide association study of caffeine metabolites provides new insights to caffeine metabolism and dietary caffeine-consumption behavior2016In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 25, no 24, p. 5472-5482Article in journal (Refereed)
    Abstract [en]

    Caffeine is the most widely consumed psychoactive substance in the world and presents with wide interindividual variation in metabolism. This variation may modify potential adverse or beneficial effects of caffeine on health. We conducted a genome-wide association study (GWAS) of plasma caffeine, paraxanthine, theophylline, theobromine and paraxanthine/caffeine ratio among up to 9,876 individuals of European ancestry from six population-based studies. A single SNP at 6p23 (near CD83) and several SNPs at 7p21 (near AHR), 15q24 (near CYP1A2) and 19q13.2 (near CYP2A6) met GW-significance (P < 5 × 10(-8)) and were associated with one or more metabolites. Variants at 7p21 and 15q24 associated with higher plasma caffeine and lower plasma paraxanthine/caffeine (slow caffeine metabolism) were previously associated with lower coffee and caffeine consumption behavior in GWAS. Variants at 19q13.2 associated with higher plasma paraxanthine/caffeine (slow paraxanthine metabolism) were also associated with lower coffee consumption in the UK Biobank (n = 94 343, P < 1.0 × 10(-6)). Variants at 2p24 (in GCKR), 4q22 (in ABCG2) and 7q11.23 (near POR) that were previously associated with coffee consumption in GWAS were nominally associated with plasma caffeine or its metabolites. Taken together, we have identified genetic factors contributing to variation in caffeine metabolism and confirm an important modulating role of systemic caffeine levels in dietary caffeine consumption behavior. Moreover, candidate genes identified encode proteins with important clinical functions that extend beyond caffeine metabolism.

  • 28. Deloukas, Panos
    et al.
    Kanoni, Stavroula
    Willenborg, Christina
    Farrall, Martin
    Assimes, Themistocles L
    Thompson, John R
    Ingelsson, Erik
    Saleheen, Danish
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Erdmann, Jeanette
    Goldstein, Benjamin A
    Stirrups, Kathleen
    König, Inke R
    Cazier, Jean-Baptiste
    Johansson, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hall, Alistair S
    Lee, Jong-Young
    Willer, Cristen J
    Chambers, John C
    Esko, Tõnu
    Folkersen, Lasse
    Goel, Anuj
    Grundberg, Elin
    Havulinna, Aki S
    Ho, Weang K
    Hopewell, Jemma C
    Eriksson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Kleber, Marcus E
    Kristiansson, Kati
    Lundmark, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Lyytikäinen, Leo-Pekka
    Rafelt, Suzanne
    Shungin, Dmitry
    Strawbridge, Rona J
    Thorleifsson, Gudmar
    Tikkanen, Emmi
    van Zuydam, Natalie
    Voight, Benjamin F
    Waite, Lindsay L
    Zhang, Weihua
    Ziegler, Andreas
    Absher, Devin
    Altshuler, David
    Balmforth, Anthony J
    Barroso, Inês
    Braund, Peter S
    Burgdorf, Christof
    Claudi-Boehm, Simone
    Cox, David
    Dimitriou, Maria
    Do, Ron
    Doney, Alex S F
    Mokhtari, Noureddine El
    Eriksson, Per
    Fischer, Krista
    Fontanillas, Pierre
    Franco-Cereceda, Anders
    Gigante, Bruna
    Groop, Leif
    Gustafsson, Stefan
    Hager, Jörg
    Hallmans, Göran
    Han, Bok-Ghee
    Hunt, Sarah E
    Kang, Hyun M
    Illig, Thomas
    Kessler, Thorsten
    Knowles, Joshua W
    Kolovou, Genovefa
    Kuusisto, Johanna
    Langenberg, Claudia
    Langford, Cordelia
    Leander, Karin
    Lokki, Marja-Liisa
    Lundmark, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    McCarthy, Mark I
    Meisinger, Christa
    Melander, Olle
    Mihailov, Evelin
    Maouche, Seraya
    Morris, Andrew D
    Müller-Nurasyid, Martina
    Nikus, Kjell
    Peden, John F
    Rayner, N William
    Rasheed, Asif
    Rosinger, Silke
    Rubin, Diana
    Rumpf, Moritz P
    Schäfer, Arne
    Sivananthan, Mohan
    Song, Ci
    Stewart, Alexandre F R
    Tan, Sian-Tsung
    Thorgeirsson, Gudmundur
    Schoot, C Ellen van der
    Wagner, Peter J
    Wells, George A
    Wild, Philipp S
    Yang, Tsun-Po
    Amouyel, Philippe
    Arveiler, Dominique
    Basart, Hanneke
    Boehnke, Michael
    Boerwinkle, Eric
    Brambilla, Paolo
    Cambien, Francois
    Cupples, Adrienne L
    de Faire, Ulf
    Dehghan, Abbas
    Diemert, Patrick
    Epstein, Stephen E
    Evans, Alun
    Ferrario, Marco M
    Ferrières, Jean
    Gauguier, Dominique
    Go, Alan S
    Goodall, Alison H
    Gudnason, Villi
    Hazen, Stanley L
    Holm, Hilma
    Iribarren, Carlos
    Jang, Yangsoo
    Kähönen, Mika
    Kee, Frank
    Kim, Hyo-Soo
    Klopp, Norman
    Koenig, Wolfgang
    Kratzer, Wolfgang
    Kuulasmaa, Kari
    Laakso, Markku
    Laaksonen, Reijo
    Lee, Ji-Young
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ouwehand, Willem H
    Parish, Sarah
    Park, Jeong E
    Pedersen, Nancy L
    Peters, Annette
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Quertermous, Thomas
    Rader, Daniel J
    Salomaa, Veikko
    Schadt, Eric
    Shah, Svati H
    Sinisalo, Juha
    Stark, Klaus
    Stefansson, Kari
    Trégouët, David-Alexandre
    Virtamo, Jarmo
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wareham, Nicholas
    Zimmermann, Martina E
    Nieminen, Markku S
    Hengstenberg, Christian
    Sandhu, Manjinder S
    Pastinen, Tomi
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Hovingh, G Kees
    Dedoussis, George
    Franks, Paul W
    Lehtimäki, Terho
    Metspalu, Andres
    Zalloua, Pierre A
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Schreiber, Stefan
    Ripatti, Samuli
    Blankenberg, Stefan S
    Perola, Markus
    Clarke, Robert
    Boehm, Bernhard O
    O'Donnell, Christopher
    Reilly, Muredach P
    März, Winfried
    Collins, Rory
    Kathiresan, Sekar
    Hamsten, Anders
    Kooner, Jaspal S
    Thorsteinsdottir, Unnur
    Danesh, John
    Palmer, Colin N A
    Roberts, Robert
    Watkins, Hugh
    Schunkert, Heribert
    Samani, Nilesh J
    Large-scale association analysis identifies new risk loci for coronary artery disease2013In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 45, no 1, p. 25-33Article in journal (Refereed)
    Abstract [en]

    Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r2 < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways.

  • 29.
    den Hoed, Marcel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Eijgelsheim, Mark
    Esko, Tonu
    Brundel, Bianca J. J. M.
    Peal, David S.
    Evans, David M.
    Nolte, Ilja M.
    Segre, Ayellet V.
    Holm, Hilma
    Handsaker, Robert E.
    Westra, Harm-Jan
    Johnson, Toby
    Isaacs, Aaron
    Yang, Jian
    Lundby, Alicia
    Zhao, Jing Hua
    Kim, Young Jin
    Go, Min Jin
    Almgren, Peter
    Bochud, Murielle
    Boucher, Gabrielle
    Cornelis, Marilyn C.
    Gudbjartsson, Daniel
    Hadley, David
    van der Harst, Pim
    Hayward, Caroline
    den Heijer, Martin
    Igl, Wilmar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Jackson, Anne U.
    Kutalik, Zoltan
    Luan, Jian'an
    Kemp, John P.
    Kristiansson, Kati
    Ladenvall, Claes
    Lorentzon, Mattias
    Montasser, May E.
    Njajou, Omer T.
    O'Reilly, Paul F.
    Padmanabhan, Sandosh
    Pourcain, Beate St.
    Rankinen, Tuomo
    Salo, Perttu
    Tanaka, Toshiko
    Timpson, Nicholas J.
    Vitart, Veronique
    Waite, Lindsay
    Wheeler, William
    Zhang, Weihua
    Draisma, Harmen H. M.
    Feitosa, Mary F.
    Kerr, Kathleen F.
    Lind, Penelope A.
    Mihailov, Evelin
    Onland-Moret, N. Charlotte
    Song, Ci
    Weedon, Michael N.
    Xie, Weijia
    Yengo, Loic
    Absher, Devin
    Albert, Christine M.
    Alonso, Alvaro
    Arking, Dan E.
    de Bakker, Paul I. W.
    Balkau, Beverley
    Barlassina, Cristina
    Benaglio, Paola
    Bis, Joshua C.
    Bouatia-Naji, Nabila
    Brage, Soren
    Chanock, Stephen J.
    Chines, Peter S.
    Chung, Mina
    Darbar, Dawood
    Dina, Christian
    Doerr, Marcus
    Elliott, Paul
    Felix, Stephan B.
    Fischer, Krista
    Fuchsberger, Christian
    de Geus, Eco J. C.
    Goyette, Philippe
    Gudnason, Vilmundur
    Harris, Tamara B.
    Hartikainen, Anna-Liisa
    Havulinna, Aki S.
    Heckbert, Susan R.
    Hicks, Andrew A.
    Hofman, Albert
    Holewijn, Suzanne
    Hoogstra-Berends, Femke
    Hottenga, Jouke-Jan
    Jensen, Majken K.
    Johansson, Asa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Junttila, Juhani
    Kaeaeb, Stefan
    Kanon, Bart
    Ketkar, Shamika
    Khaw, Kay-Tee
    Knowles, Joshua W.
    Kooner, Angrad S.
    Kors, Jan A.
    Kumari, Meena
    Milani, Lili
    Laiho, Paeivi
    Lakatta, Edward G.
    Langenberg, Claudia
    Leusink, Maarten
    Liu, Yongmei
    Luben, Robert N.
    Lunetta, Kathryn L.
    Lynch, Stacey N.
    Markus, Marcello R. P.
    Marques-Vidal, Pedro
    Leach, Irene Mateo
    McArdle, Wendy L.
    McCarroll, Steven A.
    Medland, Sarah E.
    Miller, Kathryn A.
    Montgomery, Grant W.
    Morrison, Alanna C.
    Mueller-Nurasyid, Martina
    Navarro, Pau
    Nelis, Mari
    O'Connell, Jeffrey R.
    O'Donnell, Christopher J.
    Ong, Ken K.
    Newman, Anne B.
    Peters, Annette
    Polasek, Ozren
    Pouta, Anneli
    Pramstaller, Peter P.
    Psaty, Bruce M.
    Rao, Dabeeru C.
    Ring, Susan M.
    Rossin, Elizabeth J.
    Rudan, Diana
    Sanna, Serena
    Scott, Robert A.
    Sehmi, Jaban S.
    Sharp, Stephen
    Shin, Jordan T.
    Singleton, Andrew B.
    Smith, Albert V.
    Soranzo, Nicole
    Spector, Tim D.
    Stewart, Chip
    Stringham, Heather M.
    Tarasov, Kirill V.
    Uitterlinden, Andre G.
    Vandenput, Liesbeth
    Hwang, Shih-Jen
    Whitfield, John B.
    Wijmenga, Cisca
    Wild, Sarah H.
    Willemsen, Gonneke
    Wilson, James F.
    Witteman, Jacqueline C. M.
    Wong, Andrew
    Wong, Quenna
    Jamshidi, Yalda
    Zitting, Paavo
    Boer, Jolanda M. A.
    Boomsma, Dorret I.
    Borecki, Ingrid B.
    van Duijn, Cornelia M.
    Ekelund, Ulf
    Forouhi, Nita G.
    Froguel, Philippe
    Hingorani, Aroon
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kivimaki, Mika
    Kronmal, Richard A.
    Kuh, Diana
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Martin, Nicholas G.
    Oostra, Ben A.
    Pedersen, Nancy L.
    Quertermous, Thomas
    Rotter, Jerome I.
    van der Schouw, Yvonne T.
    Verschuren, W. M. Monique
    Walker, Mark
    Albanes, Demetrius
    Arnar, David O.
    Assimes, Themistocles L.
    Bandinelli, Stefania
    Boehnke, Michael
    de Boer, Rudolf A.
    Bouchard, Claude
    Caulfield, W. L. Mark
    Chambers, John C.
    Curhan, Gary
    Cusi, Daniele
    Eriksson, Johan
    Ferrucci, Luigi
    van Gilst, Wiek H.
    Glorioso, Nicola
    de Graaf, Jacqueline
    Groop, Leif
    Gyllensten, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics.
    Hsueh, Wen-Chi
    Hu, Frank B.
    Huikuri, Heikki V.
    Hunter, David J.
    Iribarren, Carlos
    Isomaa, Bo
    Jarvelin, Marjo-Riitta
    Jula, Antti
    Kahonen, Mika
    Kiemeney, Lambertus A.
    van der Klauw, Melanie M.
    Kooner, Jaspal S.
    Kraft, Peter
    Iacoviello, Licia
    Lehtimaki, Terho
    Lokki, Marja-Liisa L.
    Mitchell, Braxton D.
    Navis, Gerjan
    Nieminen, Markku S.
    Ohlsson, Claes
    Poulter, Neil R.
    Qi, Lu
    Raitakari, Olli T.
    Rimm, Eric B.
    Rioux, John D.
    Rizzi, Federica
    Rudan, Igor
    Salomaa, Veikko
    Sever, Peter S.
    Shields, Denis C.
    Shuldiner, Alan R.
    Sinisalo, Juha
    Stanton, Alice V.
    Stolk, Ronald P.
    Strachan, David P.
    Tardif, Jean-Claude
    Thorsteinsdottir, Unnur
    Tuomilehto, Jaako
    van Veldhuisen, Dirk J.
    Virtamo, Jarmo
    Viikari, Jorma
    Vollenweider, Peter
    Waeber, Gerard
    Widen, Elisabeth
    Cho, Yoon Shin
    Olsen, Jesper V.
    Visscher, Peter M.
    Willer, Cristen
    Franke, Lude
    Erdmann, Jeanette
    Thompson, John R.
    Pfeufer, Arne
    Sotoodehnia, Nona
    Newton-Cheh, Christopher
    Ellinor, Patrick T.
    Stricker, Bruno H. Ch
    Metspalu, Andres
    Perola, Markus
    Beckmann, Jacques S.
    Smith, George Davey
    Stefansson, Kari
    Wareham, Nicholas J.
    Munroe, Patricia B.
    Sibon, Ody C. M.
    Milan, David J.
    Snieder, Harold
    Samani, Nilesh J.
    Loos, Ruth J. F.
    Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders2013In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 45, no 6, p. 621-+Article in journal (Refereed)
    Abstract [en]

    Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets.

  • 30.
    den Hoed, Marcel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Strawbridge, Rona J
    Almgren, Peter
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Axelsson, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Engström, Gunnar
    de Faire, Ulf
    Hedblad, Bo
    Humphries, Steve E
    Lindgren, Cecilia M
    Morris, Andrew P
    Östling, Gerd
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Tremoli, Elena
    Hamsten, Anders
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Melander, Olle
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    GWAS-identified loci for coronary heart disease are associated with intima-media thickness and plaque presence at the carotid artery bulb2015In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 239, no 2, p. 304-310Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Large-scale genome-wide association studies (GWAS) have so far identified 45 loci that are robustly associated with coronary heart disease (CHD) in data from adult men and women of European descent.

    OBJECTIVES: To examine whether the CHD-associated loci are associated with measures of atherosclerosis in data from up to 9582 individuals of European ancestry.

    METHODS: Forty-five SNPs representing the CHD-associated loci were genotyped in middle-aged to elderly individuals of European descent from four independent population-based studies (IMPROVE, MDC-CC, ULSAM and PIVUS). Intima-media thickness (IMT) was measured by external B-mode ultrasonography at the far wall of the bulb (sinus) and common carotid artery. Plaque presence was defined as a maximal IMT of the bulb >1.5 mm. We meta-analysed single-SNP associations across the four studies, and combined them in a genetic predisposition score. We subsequently examined the association of the genetic predisposition score with prevalent CHD and the three indices of atherosclerosis, adjusting for sex, age and Framingham risk factors.

    RESULTS: As anticipated, the genetic predisposition score was associated with prevalent CHD, with each additional risk allele increasing the odds of disease by 5.5% (p = 4.1 × 10(-6)). Moreover, each additional CHD-risk allele across the 45 loci was associated with a 0.24% increase in IMT (p = 4.0 × 10(-3)), and with a 2.8% increased odds of plaque presence (p = 7.4 × 10(-6)) at the far wall of the bulb. The genetic predisposition score was not associated with IMT of the common carotid artery (p = 0.47).

    CONCLUSIONS: Our results suggest that the association between the 45 previously identified loci and CHD at least partly acts through atherosclerosis.

  • 31. Dimas, Antigone S.
    et al.
    Lagou, Vasiliki
    Barker, Adam
    Knowles, Joshua W.
    Maegi, Reedik
    Hivert, Marie-France
    Benazzo, Andrea
    Rybin, Denis
    Jackson, Anne U.
    Stringham, Heather M.
    Song, Ci
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Fischer-Rosinsky, Antje
    Boesgaard, Trine Wellov
    Grarup, Niels
    Abbasi, Fahim A.
    Assimes, Themistocles L.
    Hao, Ke
    Yang, Xia
    Lecoeur, Cecile
    Barroso, Ines
    Bonnycastle, Lori L.
    Boettcher, Yvonne
    Bumpstead, Suzannah
    Chines, Peter S.
    Erdos, Michael R.
    Graessler, Jurgen
    Kovacs, Peter
    Morken, Mario A.
    Narisu, Narisu
    Payne, Felicity
    Stancakova, Alena
    Swift, Amy J.
    Toenjes, Anke
    Bornstein, Stefan R.
    Cauchi, Stephane
    Froguel, Philippe
    Meyre, David
    Schwarz, Peter E. H.
    Haering, Hans-Ulrich
    Smith, Ulf
    Boehnke, Michael
    Bergman, Richard N.
    Collins, Francis S.
    Mohlke, Karen L.
    Tuomilehto, Jaakko
    Quertemous, Thomas
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Hansen, Torben
    Pedersen, Oluf
    Walker, Mark
    Pfeiffer, Andreas F. H.
    Spranger, Joachim
    Stumvoll, Michael
    Meigs, James B.
    Wareham, Nicholas J.
    Kuusisto, Johanna
    Laakso, Markku
    Langenberg, Claudia
    Dupuis, Josee
    Watanabe, Richard M.
    Florez, Jose C.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    McCarthy, Mark I.
    Prokopenko, Inga
    Impact of Type 2 Diabetes Susceptibility Variants on Quantitative Glycemic Traits Reveals Mechanistic Heterogeneity2014In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 63, no 6, p. 2158-2171Article in journal (Refereed)
    Abstract [en]

    Patients with established type 2 diabetes display both beta-cell dysfunction and insulin resistance. To define fundamental processes leading to the diabetic state, we examined the relationship between type 2 diabetes risk variants at 37 established susceptibility loci, and indices of proinsulin processing, insulin secretion, and insulin sensitivity. We included data from up to 58,614 nondiabetic subjects with basal measures and 17,327 with dynamic measures. We used additive genetic models with adjustment for sex, age, and BMI, followed by fixed-effects, inverse-variance meta-analyses. Cluster analyses grouped risk loci into five major categories based on their relationship to these continuous glycemic phenotypes. The first cluster (PPARG, KLF14, IRS1, GCKR) was characterized by primary effects on insulin sensitivity. The second cluster (MTNR1B, GCK) featured risk alleles associated with reduced insulin secretion and fasting hyperglycemia. ARAP1 constituted a third cluster characterized by defects in insulin processing. A fourth cluster (TCF712, SLC30A8, HHEX/IDE, CDKAL1, CDKN2A/2B) was defined by loci influencing insulin processing and secretion without a detectable change in fasting glucose levels. The final group contained 20 risk loci with no clear-cut associations to continuous glycemic traits. By assembling extensive data on continuous glycemic traits, we have exposed the diverse mechanisms whereby type 2 diabetes risk variants impact disease predisposition.

  • 32. Do, Ron
    et al.
    Willer, Cristen J.
    Schmidt, Ellen M.
    Sengupta, Sebanti
    Gao, Chi
    Peloso, Gina M.
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kanoni, Stavroula
    Ganna, Andrea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Chen, Jin
    Buchkovich, Martin L.
    Mora, Samia
    Beckmann, Jacques S.
    Bragg-Gresham, Jennifer L.
    Chang, Hsing-Yi
    Demirkan, Ayse
    Den Hertog, Heleen M.
    Donnelly, Louise A.
    Ehret, Georg B.
    Esko, Tonu
    Feitosa, Mary F.
    Ferreira, Teresa
    Fischer, Krista
    Fontanillas, Pierre
    Fraser, Ross M.
    Freitag, Daniel F.
    Gurdasani, Deepti
    Heikkila, Kauko
    Hyppoenen, Elina
    Isaacs, Aaron
    Jackson, Anne U.
    Johansson, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Johnson, Toby
    Kaakinen, Marika
    Kettunen, Johannes
    Kleber, Marcus E.
    Li, Xiaohui
    Luan, Jian'an
    Lyytikainen, Leo-Pekka
    Magnusson, Patrik K. E.
    Mangino, Massimo
    Mihailov, Evelin
    Montasser, May E.
    Mueller-Nurasyid, Martina
    Nolte, Ilja M.
    O'Connell, Jeffrey R.
    Palmer, Cameron D.
    Perola, Markus
    Petersen, Ann-Kristin
    Sanna, Serena
    Saxena, Richa
    Service, Susan K.
    Shah, Sonia
    Shungin, Dmitry
    Sidore, Carlo
    Song, Ci
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Strawbridge, Rona J.
    Surakka, Ida
    Tanaka, Toshiko
    Teslovich, Tanya M.
    Thorleifsson, Gudmar
    Van den Herik, Evita G.
    Voight, Benjamin F.
    Volcik, Kelly A.
    Waite, Lindsay L.
    Wong, Andrew
    Wu, Ying
    Zhang, Weihua
    Absher, Devin
    Asiki, Gershim
    Barroso, Ines
    Been, Latonya F.
    Bolton, Jennifer L.
    Bonnycastle, Lori L.
    Brambilla, Paolo
    Burnett, Mary S.
    Cesana, Giancarlo
    Dimitriou, Maria
    Doney, Alex S. F.
    Doering, Angela
    Elliott, Paul
    Epstein, Stephen E.
    Eyjolfsson, Gudmundur Ingi
    Gigante, Bruna
    Goodarzi, Mark O.
    Grallert, Harald
    Gravito, Martha L.
    Groves, Christopher J.
    Hallmans, Goran
    Hartikainen, Anna-Liisa
    Hayward, Caroline
    Hernandez, Dena
    Hicks, Andrew A.
    Holm, Hilma
    Hung, Yi-Jen
    Illig, Thomas
    Jones, Michelle R.
    Kaleebu, Pontiano
    Kastelein, John J. P.
    Khaw, Kay-Tee
    Kim, Eric
    Klopp, Norman
    Komulainen, Pirjo
    Kumari, Meena
    Langenberg, Claudia
    Lehtimaki, Terho
    Lin, Shih-Yi
    Lindstrom, Jaana
    Loos, Ruth J. F.
    Mach, Francois
    McArdle, Wendy L.
    Meisinger, Christa
    Mitchell, Braxton D.
    Mueller, Gabrielle
    Nagaraja, Ramaiah
    Narisu, Narisu
    Nieminen, Tuomo V. M.
    Nsubuga, Rebecca N.
    Olafsson, Isleifur
    Ong, Ken K.
    Palotie, Aarno
    Papamarkou, Theodore
    Pomilla, Cristina
    Pouta, Anneli
    Rader, Daniel J.
    Reilly, Muredach P.
    Ridker, Paul M.
    Rivadeneira, Fernando
    Rudan, Igor
    Ruokonen, Aimo
    Samani, Nilesh
    Scharnagl, Hubert
    Seeley, Janet
    Silander, Kaisa
    Stancakova, Alena
    Stirrups, Kathleen
    Swift, Amy J.
    Tiret, Laurence
    Uitterlinden, Andre G.
    van Pelt, L. Joost
    Vedantam, Sailaja
    Wainwright, Nicholas
    Wijmenga, Cisca
    Wild, Sarah H.
    Willemsen, Gonneke
    Wilsgaard, Tom
    Wilson, James F.
    Young, Elizabeth H.
    Zhao, Jing Hua
    Adair, Linda S.
    Arveiler, Dominique
    Assimes, Themistocles L.
    Bandinelli, Stefania
    Bennett, Franklyn
    Bochud, Murielle
    Boehm, Bernhard O.
    Boomsma, Dorret I.
    Borecki, Ingrid B.
    Bornstein, Stefan R.
    Bovet, Pascal
    Burnier, Michel
    Campbell, Harry
    Chakravarti, Aravinda
    Chambers, John C.
    Chen, Yii-Der Ida
    Collins, Francis S.
    Cooper, Richard S.
    Danesh, John
    Dedoussis, George
    de Faire, Ulf
    Feranil, Alan B.
    Ferrieres, Jean
    Ferrucci, Luigi
    Freimer, Nelson B.
    Gieger, Christian
    Groop, Leif C.
    Gudnason, Vilmundur
    Gyllensten, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hamsten, Anders
    Harris, Tamara B.
    Hingorani, Aroon
    Hirschhorn, Joel N.
    Hofman, Albert
    Hovingh, G. Kees
    Hsiung, Chao Agnes
    Humphries, Steve E.
    Hunt, Steven C.
    Hveem, Kristian
    Iribarren, Carlos
    Jarvelin, Marjo-Riitta
    Jula, Antti
    Kahonen, Mika
    Kaprio, Jaakko
    Kesaniemi, Antero
    Kivimaki, Mika
    Kooner, Jaspal S.
    Koudstaal, Peter J.
    Krauss, Ronald M.
    Kuh, Diana
    Kuusisto, Johanna
    Kyvik, Kirsten O.
    Laakso, Markku
    Lakka, Timo A.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lindgren, Cecilia M.
    Martin, Nicholas G.
    Maerz, Winfried
    McCarthy, Mark I.
    McKenzie, Colin A.
    Meneton, Pierre
    Metspalu, Andres
    Moilanen, Leena
    Morris, Andrew D.
    Munroe, Patricia B.
    Njolstad, Inger
    Pedersen, Nancy L.
    Power, Chris
    Pramstaller, Peter P.
    Price, Jackie F.
    Psaty, Bruce M.
    Quertermous, Thomas
    Rauramaa, Rainer
    Saleheen, Danish
    Salomaa, Veikko
    Sanghera, Dharambir K.
    Saramies, Jouko
    Schwarz, Peter E. H.
    Sheu, Wayne H-H
    Shuldiner, Alan R.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Spector, Tim D.
    Stefansson, Kari
    Strachan, David P.
    Tayo, Bamidele O.
    Tremoli, Elena
    Tuomilehto, Jaakko
    Uusitupa, Matti
    van Duijn, Cornelia M.
    Vollenweider, Peter
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Wareham, Nicholas J.
    Whitfield, John B.
    Wolffenbuttel, Bruce H. R.
    Altshuler, David
    Ordovas, Jose M.
    Boerwinkle, Eric
    Palmer, Colin N. A.
    Thorsteinsdottir, Unnur
    Chasman, Daniel I.
    Rotter, Jerome I.
    Franks, Paul W.
    Ripatti, Samuli
    Cupples, L. Adrienne
    Sandhu, Manjinder S.
    Rich, Stephen S.
    Boehnke, Michael
    Deloukas, Panos
    Mohlke, Karen L.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Abecasis, Goncalo R.
    Daly, Mark J.
    Neale, Benjamin M.
    Kathiresan, Sekar
    Common variants associated with plasma triglycerides and risk for coronary artery disease2013In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 45, no 11, p. 1345-+Article in journal (Refereed)
    Abstract [en]

    Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.

  • 33.
    Dumanski, Jan P.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Rasi, Chiara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lönn, Mikael
    Södertörn University, School of Life Sciences, Biology, Huddinge, Sweden.
    Davies, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ingelsson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Magnusson, Patrik K. E.
    Department of Economics, Stockholm School of Economics, Stockholm, Sweden.
    Lindgren, Cecilia M.
    Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK;Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts, USA.
    Morris, Andrew P.
    Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK;Department of Biostatistics, University of Liverpool, Liverpool, UK.
    Cesarini, David
    Center for Experimental Social Science, New York University, New York, NY 10012, USA.
    Johannesson, Magnus
    Department of Economics, Stockholm School of Economics, Stockholm, Sweden.
    Tiensuu Janson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine oncology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Pedersen, Nancy L.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Forsberg, Lars A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mutagenesis: smoking is associated with mosaic loss of chromosome Y2015In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 347, no 6217, p. 81-83Article in journal (Refereed)
    Abstract [en]

    Tobacco smoking is a risk factor for numerous disorders, including cancers affecting organs outside the respiratory tract. Epidemiological data suggest that smoking is a greater risk factor for these cancers in males compared to females. This observation, together with the fact that males have a higher incidence of and mortality from most non-sex-specific cancers, remains unexplained. Loss of chromosome Y (LOY) in blood cells is associated with increased risk of nonhematological tumors. We demonstrate here that smoking is associated with LOY in blood cells in three independent cohorts [TwinGene: odds ratio (OR) = 4.3, 95% CI = 2.8-6.7; ULSAM: OR = 2.4, 95% CI = 1.6-3.6; and PIVUS: OR = 3.5, 95% CI = 1.4-8.4] encompassing a total of 6014 men. The data also suggest that smoking has a transient and dose-dependent mutagenic effect on LOY status. The finding that smoking induces LOY thus links a preventable risk factor with the most common acquired human mutation.

  • 34.
    Ek, Weronica E.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Tobi, Elmar W
    Ahsan, Muhammad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lampa, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ponzi, Erica
    Kyrtopoulos, Soterios A
    Georgiadis, Panagiotis
    Lumey, L H
    Heijmans, Bastiaan T
    Botsivali, Maria
    Bergdahl, Ingvar A
    Karlsson, Torgny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Rask-Andersen, Mathias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Palli, Domenico
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA.
    Hedman, Åsa K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nilsson, Lena M
    Vineis, Paolo
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Flanagan, James M
    Johansson, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Tea and coffee consumption in relation to DNA methylation in four European cohorts2017In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 26, no 16, p. 3221-3231Article in journal (Refereed)
    Abstract [en]

    Lifestyle factors, such as food choices and exposure to chemicals, can alter DNA methylation and lead to changes in gene activity. Two such exposures with pharmacologically active components are coffee and tea consumption. Both coffee and tea have been suggested to play an important role in modulating disease-risk in humans by suppressing tumour progression, decreasing inflammation and influencing estrogen metabolism. These mechanisms may be mediated by changes in DNA methylation. To investigate if DNA methylation in blood is associated with coffee and tea consumption, we performed a genome-wide DNA methylation study for coffee and tea consumption in four European cohorts (N = 3,096). DNA methylation was measured from whole blood at 421,695 CpG sites distributed throughout the genome and analysed in men and women both separately and together in each cohort. Meta-analyses of the results and additional regional-level analyses were performed. After adjusting for multiple testing, the meta-analysis revealed that two individual CpG-sites, mapping to DNAJC16 and TTC17, were differentially methylated in relation to tea consumption in women. No individual sites were associated with men or with the sex-combined analysis for tea or coffee. The regional analysis revealed that 28 regions were differentially methylated in relation to tea consumption in women. These regions contained genes known to interact with estradiol metabolism and cancer. No significant regions were found in the sex-combined and male-only analysis for either tea or coffee consumption.

  • 35. Elks, Cathy E
    et al.
    Perry, John R B
    Sulem, Patrick
    Chasman, Daniel I
    Franceschini, Nora
    He, Chunyan
    Lunetta, Kathryn L
    Visser, Jenny A
    Byrne, Enda M
    Cousminer, Diana L
    Gudbjartsson, Daniel F
    Esko, Tõnu
    Feenstra, Bjarke
    Hottenga, Jouke-Jan
    Koller, Daniel L
    Kutalik, Zoltán
    Lin, Peng
    Mangino, Massimo
    Marongiu, Mara
    McArdle, Patrick F
    Smith, Albert V
    Stolk, Lisette
    van Wingerden, Sophie H
    Zhao, Jing Hua
    Albrecht, Eva
    Corre, Tanguy
    Ingelsson, Erik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
    Hayward, Caroline
    Magnusson, Patrik K E
    Smith, Erin N
    Ulivi, Shelia
    Warrington, Nicole M
    Zgaga, Lina
    Alavere, Helen
    Amin, Najaf
    Aspelund, Thor
    Bandinelli, Stefania
    Barroso, Inês
    Berenson, Gerald S
    Bergmann, Sven
    Blackburn, Hannah
    Boerwinkle, Eric
    Buring, Julie E
    Busonero, Fabio
    Campbell, Harry
    Chanock, Stephen J
    Chen, Wei
    Cornelis, Marilyn C
    Couper, David
    Coviello, Andrea D
    d'Adamo, Pio
    de Faire, Ulf
    de Geus, Eco J C
    Deloukas, Panos
    Döring, Angela
    Smith, George Davey
    Easton, Douglas F
    Eiriksdottir, Gudny
    Emilsson, Valur
    Eriksson, Johan
    Ferrucci, Luigi
    Folsom, Aaron R
    Foroud, Tatiana
    Garcia, Melissa
    Gasparini, Paolo
    Geller, Frank
    Gieger, Christian
    Gudnason, Vilmundur
    Hall, Per
    Hankinson, Susan E
    Ferreli, Liana
    Heath, Andrew C
    Hernandez, Dena G
    Hofman, Albert
    Hu, Frank B
    Illig, Thomas
    Järvelin, Marjo-Riitta
    Johnson, Andrew D
    Karasik, David
    Khaw, Kay-Tee
    Kiel, Douglas P
    Kilpeläinen, Tuomas O
    Kolcic, Ivana
    Kraft, Peter
    Launer, Lenore J
    Laven, Joop S E
    Li, Shengxu
    Liu, Jianjun
    Levy, Daniel
    Martin, Nicholas G
    McArdle, Wendy L
    Melbye, Mads
    Mooser, Vincent
    Murray, Jeffrey C
    Murray, Sarah S
    Nalls, Michael A
    Navarro, Pau
    Nelis, Mari
    Ness, Andrew R
    Northstone, Kate
    Oostra, Ben A
    Peacock, Munro
    Palmer, Lyle J
    Palotie, Aarno
    Paré, Guillaume
    Parker, Alex N
    Pedersen, Nancy L
    Peltonen, Leena
    Pennell, Craig E
    Pharoah, Paul
    Polasek, Ozren
    Plump, Andrew S
    Pouta, Anneli
    Porcu, Eleonora
    Rafnar, Thorunn
    Rice, John P
    Ring, Susan M
    Rivadeneira, Fernando
    Rudan, Igor
    Sala, Cinzia
    Salomaa, Veikko
    Sanna, Serena
    Schlessinger, David
    Schork, Nicholas J
    Scuteri, Angelo
    Segrè, Ayellet V
    Shuldiner, Alan R
    Soranzo, Nicole
    Sovio, Ulla
    Srinivasan, Sathanur R
    Strachan, David P
    Tammesoo, Mar-Liis
    Tikkanen, Emmi
    Toniolo, Daniela
    Tsui, Kim
    Tryggvadottir, Laufey
    Tyrer, Jonathon
    Uda, Manuela
    van Dam, Rob M
    van Meurs, Joyce B J
    Vollenweider, Peter
    Waeber, Gerard
    Wareham, Nicholas J
    Waterworth, Dawn M
    Weedon, Michael N
    Wichmann, H Erich
    Willemsen, Gonneke
    Wilson, James F
    Wright, Alan F
    Young, Lauren
    Zhai, Guangju
    Zhuang, Wei Vivian
    Bierut, Laura J
    Boomsma, Dorret I
    Boyd, Heather A
    Crisponi, Laura
    Demerath, Ellen W
    van Duijn, Cornelia M
    Econs, Michael J
    Harris, Tamara B
    Hunter, David J
    Loos, Ruth J F
    Metspalu, Andres
    Montgomery, Grant W
    Ridker, Paul M
    Spector, Tim D
    Streeten, Elizabeth A
    Stefansson, Kari
    Thorsteinsdottir, Unnur
    Uitterlinden, André G
    Widen, Elisabeth
    Murabito, Joanne M
    Ong, Ken K
    Murray, Anna
    Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies2010In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 42, no 12, p. 1077-85Article in journal (Refereed)
    Abstract [en]

    To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10⁻⁶⁰) and 9q31.2 (P = 2.2 × 10⁻³³), we identified 30 new menarche loci (all P < 5 × 10⁻⁸) and found suggestive evidence for a further 10 loci (P < 1.9 × 10⁻⁶). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.

  • 36. Fall, T.
    et al.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology, Diabetes and Metabolism.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    The role of obesity-related genetic loci in insulin sensitivity2012In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 29, no 7, p. E62-E66Article in journal (Refereed)
    Abstract [en]

    Aims Despite rapid advancements and many new diabetes susceptibility loci found in the past few years, few genetic variants associated with insulin sensitivity have been described, potentially attributable to the lack of larger cohorts examined with gold standard methods for insulin sensitivity assessment. There is a strong link between obesity and insulin sensitivity, and we hypothesized that known obesity susceptibility loci may act via effects on insulin sensitivity. Methods A cohort of 71-year-old men without diabetes (Uppsala Longitudinal Study of Adult Men) underwent a euglycaemichyperinsulinaemic clamp and genotyping for genetic variants representing 32 loci recently reported to be associated with BMI (n = 926). The effect of these loci on the insulin sensitivity index (M/I ratio) was examined using linear regression. An in silico replication was performed in publically available data for the three top single-nucleotide polymorphisms from the Meta-Analyses of Glucose and Insulin-related traits Consortium analyses of homeostasis model assessment of insulin resistance (n = 37 037). Results Three loci (SH2B1, MTCH2 and NEGR1) were associated with decreased insulin sensitivity at a nominal significance (P = 0.05) after adjustment for BMI, but did not hold for multiple comparison correction. SH2B1 rs7359397 was also associated with homeostasis model assessment of insulin resistance in the Meta-Analyses of Glucose and Insulin-related traits Consortium data set (P = 3.9 x 10(3)). Conclusions Our study supports earlier reports of SH2B1 to be of importance in insulin sensitivity and, in addition, suggests potential roles of NEGR1 and MTCH2.

  • 37.
    Fall, Tove
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hägg, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Maegi, Reedik
    Ploner, Alexander
    Fischer, Krista
    Horikoshi, Momoko
    Sarin, Antti-Pekka
    Thorleifsson, Gudmar
    Ladenvall, Claes
    Kals, Mart
    Kuningas, Maris
    Draisma, Harmen H. M.
    Ried, Janina S.
    van Zuydam, Natalie R.
    Huikari, Ville
    Mangino, Massimo
    Sonestedt, Emily
    Benyamin, Beben
    Nelson, Christopher P.
    Rivera, Natalia V.
    Kristiansson, Kati
    Shen, Huei-yi
    Havulinna, Aki S.
    Dehghan, Abbas
    Donnelly, Louise A.
    Kaakinen, Marika
    Nuotio, Marja-Liisa
    Robertson, Neil
    de Bruijn, Renee F. A. G.
    Ikram, M. Arfan
    Amin, Najaf
    Balmforth, Anthony J.
    Braund, Peter S.
    Doney, Alexander S. F.
    Doering, Angela
    Elliott, Paul
    Esko, Tonu
    Franco, Oscar H.
    Gretarsdottir, Solveig
    Hartikainen, Anna-Liisa
    Heikkila, Kauko
    Herzig, Karl-Heinz
    Holm, Hilma
    Hottenga, Jouke Jan
    Hypponen, Elina
    Illig, Thomas
    Isaacs, Aaron
    Isomaa, Bo
    Karssen, Lennart C.
    Kettunen, Johannes
    Koenig, Wolfgang
    Kuulasmaa, Kari
    Laatikainen, Tiina
    Laitinen, Jaana
    Lindgren, Cecilia
    Lyssenko, Valeriya
    Laara, Esa
    Rayner, Nigel W.
    Mannisto, Satu
    Pouta, Anneli
    Rathmann, Wolfgang
    Rivadeneira, Fernando
    Ruokonen, Aimo
    Savolainen, Markku J.
    Sijbrands, Eric J. G.
    Small, Kerrin S.
    Smit, Jan H.
    Steinthorsdottir, Valgerdur
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Taanila, Anja
    Tobin, Martin D.
    Uitterlinden, Andre G.
    Willems, Sara M.
    Willemsen, Gonneke
    Witteman, Jacqueline
    Perola, Markus
    Evans, Alun
    Ferrieres, Jean
    Virtamo, Jarmo
    Kee, Frank
    Tregouet, David-Alexandre
    Arveiler, Dominique
    Amouyel, Philippe
    Ferrario, Marco M.
    Brambilla, Paolo
    Hall, Alistair S.
    Heath, AndrewC.
    Madden, Pamela A. F.
    Martin, Nicholas G.
    Montgomery, Grant W.
    Whitfield, John B.
    Jula, Antti
    Knekt, Paul
    Oostra, Ben
    van Duijn, Cornelia M.
    Penninx, Brenda W. J. H.
    Smith, George Davey
    Kaprio, Jaakko
    Samani, Nilesh J.
    Gieger, Christian
    Peters, Annette
    Wichmann, H. -Erich
    Boomsma, Dorret I.
    de Geus, Eco J. C.
    Tuomi, TiinaMaija
    Power, Chris
    Hammond, Christopher J.
    Spector, Tim D.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Orho-Melander, Marju
    Palmer, Colin Neil Alexander
    Morris, Andrew D.
    Groop, Leif
    Jarvelin, Marjo-Riitta
    Salomaa, Veikko
    Vartiainen, Erkki
    Hofman, Albert
    Ripatti, Samuli
    Metspalu, Andres
    Thorsteinsdottir, Unnur
    Stefansson, Kari
    Pedersen, Nancy L.
    McCarthy, Mark I.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Prokopenko, Inga
    The Role of Adiposity in Cardiometabolic Traits: A Mendelian Randomization Analysis2013In: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 10, no 6, p. e1001474-Article in journal (Refereed)
    Abstract [en]

    Background: The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach. Methods and Findings: We used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV) for body mass index (BMI) in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses. Age-and sex-adjusted regression models were fitted to test for association between (i) rs9939609 and BMI (n = 198,502), (ii) rs9939609 and 24 traits, and (iii) BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI-trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03-1.39) and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1-1.4; all p<0.05). For quantitative traits, our results provide novel evidence for a causal effect of adiposity on the liver enzymes alanine aminotransferase and gamma-glutamyl transferase and confirm previous reports of a causal effect of adiposity on systolic and diastolic blood pressure, fasting insulin, 2-h post-load glucose from the oral glucose tolerance test, C-reactive protein, triglycerides, and high-density lipoprotein cholesterol levels (all p<0.05). The estimated causal effects were in agreement with traditional observational measures in all instances except for type 2 diabetes, where the causal estimate was larger than the observational estimate (p = 0.001). Conclusions: We provide novel evidence for a causal relationship between adiposity and heart failure as well as between adiposity and increased liver enzymes.

  • 38.
    Fall, Tove
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hägg, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ploner, Alexander
    Mägi, Reedik
    Fischer, Krista
    Draisma, Harmen H M
    Sarin, Antti-Pekka
    Benyamin, Beben
    Ladenvall, Claes
    Åkerlund, Mikael
    Kals, Mart
    Esko, Tõnu
    Nelson, Christopher P
    Kaakinen, Marika
    Huikari, Ville
    Mangino, Massimo
    Meirhaeghe, Aline
    Kristiansson, Kati
    Nuotio, Marja-Liisa
    Kobl, Michael
    Grallert, Harald
    Dehghan, Abbas
    Kuningas, Maris
    de Vries, Paul S
    de Bruijn, Renée F A G
    Willems, Sara M
    Heikkilä, Kauko
    Silventoinen, Karri
    Pietiläinen, Kirsi H
    Legry, Vanessa
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Goumidi, Louisa
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Strauch, Konstantin
    Koenig, Wolfgang
    Lichtner, Peter
    Herder, Christian
    Palotie, Aarno
    Menni, Cristina
    Uitterlinden, André G
    Kuulasmaa, Kari
    Havulinna, Aki S
    Moreno, Luis A
    Gonzalez-Gross, Marcela
    Evans, Alun
    Tregouet, David-Alexandre
    Yarnell, John W G
    Virtamo, Jarmo
    Ferrières, Jean
    Veronesi, Giovanni
    Perola, Markus
    Arveiler, Dominique
    Brambilla, Paolo
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Kaprio, Jaakko
    Hofman, Albert
    Stricker, Bruno H
    van Duijn, Cornelia M
    Ikram, M Arfan
    Franco, Oscar H
    Cottel, Dominique
    Dallongeville, Jean
    Hall, Alistair S
    Jula, Antti
    Tobin, Martin D
    Penninx, Brenda W
    Peters, Annette
    Gieger, Christian
    Samani, Nilesh J
    Montgomery, Grant W
    Whitfield, John B
    Martin, Nicholas G
    Groop, Leif
    Spector, Tim D
    Magnusson, Patrik K
    Amouyel, Philippe
    Boomsma, Dorret I
    Nilsson, Peter M
    Järvelin, Marjo-Riitta
    Lyssenko, Valeriya
    Metspalu, Andres
    Strachan, David P
    Salomaa, Veikko
    Ripatti, Samuli
    Pedersen, Nancy L
    Prokopenko, Inga
    McCarthy, Mark I
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Age- and sex-specific causal effects of adiposity on cardiovascular risk factors2015In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 64, no 5, p. 1841-1852Article in journal (Refereed)
    Abstract [en]

    Observational studies have reported different effects of adiposity on cardiovascular risk factors across age and sex. Since cardiovascular risk factors are enriched in obese individuals, it has not been easy to dissect the effects of adiposity from those of other risk factors. We used a Mendelian randomization approach, applying a set of 32 genetic markers to estimate the causal effect of adiposity on blood pressure, glycemic indices, circulating lipid levels, and markers of inflammation and liver disease in up to 67,553 individuals. All analyses were stratified by age (cutoff 55 years of age) and sex. The genetic score was associated with BMI in both nonstratified analysis (P = 2.8 × 10(-107)) and stratified analyses (all P < 3.3 × 10(-30)). We found evidence of a causal effect of adiposity on blood pressure, fasting levels of insulin, C-reactive protein, interleukin-6, HDL cholesterol, and triglycerides in a nonstratified analysis and in the <55-year stratum. Further, we found evidence of a smaller causal effect on total cholesterol (P for difference = 0.015) in the ≥55-year stratum than in the <55-year stratum, a finding that could be explained by biology, survival bias, or differential medication. In conclusion, this study extends previous knowledge of the effects of adiposity by providing sex- and age-specific causal estimates on cardiovascular risk factors.

  • 39.
    Fall, Tove
    et al.
    Dept. of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 77 Stockholm, Sweden.
    Ingelsson, Erik
    Dept. of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 77 Stockholm, Sweden.
    Genome-wide association studies of obesity and metabolic syndrome2014In: Molecular and Cellular Endocrinology, ISSN 0303-7207, E-ISSN 1872-8057, Vol. 382, no 1, p. 740-757Article in journal (Refereed)
    Abstract [en]

    Until just a few years ago, the genetic determinants of obesity and metabolic syndrome were largely unknown, with the exception of a few forms of monogenic extreme obesity. Since genome-wide association studies (GWAS) became available, large advances have been made. The first single nucleotide polymorphism robustly associated with increased body mass index (BMI) was in 2007 mapped to a gene with for the time unknown function. This gene, now known as fat mass and obesity associated (FTO) has been repeatedly replicated in several ethnicities and is affecting obesity by regulating appetite. Since the first report from a GWAS of obesity, an increasing number of markers have been shown to be associated with BMI, other measures of obesity or fat distribution and metabolic syndrome. This systematic review of obesity GWAS will summarize genome-wide significant findings for obesity and metabolic syndrome and briefly give a few suggestions of what is to be expected in the next few years.

  • 40.
    Fall, Tove
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Lundholm, Cecilia
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Ortqvist, Anne K.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Fall, Katja
    Orebro Univ Hosp, Clin Epidemiol & Biostat, Orebro, Sweden.;Univ Orebro, Sch Hlth & Med Sci, SE-70182 Orebro, Sweden..
    Fang, Fang
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Hedhammar, Ake
    Swedish Univ Agr Sci, Dept Clin Sci, Uppsala, Sweden..
    Kampe, Olle
    Karolinska Inst, Dept Med, Ctr Mol Med, Stockholm, Sweden..
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Almqvist, Catarina
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.;Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Lung & Allergy Unit, Stockholm, Sweden..
    Early Exposure to Dogs and Farm Animals and the Risk of Childhood Asthma2015In: JAMA pediatrics, ISSN 2168-6203, E-ISSN 2168-6211, Vol. 169, no 11, article id e153219Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE The association between early exposure to animals and childhood asthma is not clear, and previous studies have yielded contradictory results. OBJECTIVE To determine whether exposure to dogs and farm animals confers a risk of asthma. DESIGN, SETTING AND PARTICIPANTS In a nationwide cohort study, the association between early exposure to dogs and farm animals and the risk of asthma was evaluated and included all children born in Sweden from January 1, 2001, to December 31, 2010 (N = 1 011 051), using registry data on dog and farm registration, asthma medication, diagnosis, and confounders for parents and their children. The association was assessed as the odds ratio (OR) for a current diagnosis of asthma at age 6 years for school-aged children and as the hazard ratio (HR) for incident asthma at ages 1 to 5 years for preschool-aged children. Data were analyzed from January 1, 2007, to September 30, 2012. EXPOSURES Living with a dog or farm animal. MAIN OUTCOMES AND MEASURES Childhood asthma diagnosis and medication used. RESULTS Of the 1 011 051 children born during the study period, 376 638 preschool-aged (53 460 [14.2%] exposed to dogs and 1729 [0.5%] exposed to farm animals) and 276 298 school-aged children (22 629 [8.2%] exposed to dogs and 958 [0.3%] exposed to farm animals) were included in the analyses. Of these, 18 799 children (5.0%) in the preschool-aged children's cohort experienced an asthmatic event before baseline, and 28 511 cases of asthma and 906 071 years at risk were recorded during follow-up (incidence rate, 3.1 cases per 1000 years at risk). In the school-aged children's cohort, 11 585 children (4.2%) experienced an asthmatic event during the seventh year of life. Dog exposure during the first year of life was associated with a decreased risk of asthma in school-aged children (OR, 0.87; 95% CI, 0.81-0.93) and in preschool-aged children 3 years or older (HR, 0.90; 95% CI, 0.83-0.99) but not in children younger than 3 years (HR, 1.03; 95% CI, 1.00-1.07). Results were comparable when analyzing only first-born children. Farm animal exposure was associated with a reduced risk of asthma in both school-aged children and preschool-aged children (OR, 0.48; 95% CI, 0.31-0.76, and HR, 0.69; 95% CI, 0.56-0.84), respectively. CONCLUSIONS AND RELEVANCE In this study, the data support the hypothesis that exposure to dogs and farm animals during the first year of life reduces the risk of asthma in children at age 6 years. This information might be helpful in decision making for families and physicians on the appropriateness and timing of early animal exposure.

  • 41. Fall, Tove
    et al.
    Shiue, Ivy
    af Geijerstam, Per Bergea
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Relations of circulating vitamin D concentrations with left ventricular geometry and function2012In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 14, no 9, p. 985-991Article in journal (Refereed)
    Abstract [en]

    Vitamin D deficiency has been associated with risk of overt cardiovascular disease (CVD), but associations with subclinical disease are not well characterized. Hence, we examined associations of circulating vitamin D concentrations and left ventricular (LV) geometry and function by echocardiography at baseline and after 5 years in a community-based study. In the PIVUS study, we measured serum 25-dihydroxyvitamin-D (25-OH D) at age 70 and performed echocardiography including LV mass, wall thickness, end-diastolic diameter, end-systolic diameter (LVESD), left atrial diameter, fractional shortening, ejection fraction, isovolumic relaxation time, and E/A ratio at both age 70 and 75. We included 870 participants (52 women) without prior myocardial infarctions, heart failure, or prevalent valvular disease. After adjusting for potential confounders, 25-OH D at baseline was found to be significantly associated with LVESD, fractional shortening, and ejection fraction (, 0.42 mm, P 0.03; , 0.70, P 0.03; and , 0.91 P 0.01, respectively), per 1 SD increase in 25-OH D (SD 20 nmol/L) at baseline. In longitudinal analyses, vitamin D levels at baseline were not significantly associated with change in LV geometry and function after 5 years. In our community-based study among the elderly, we found higher circulating vitamin D concentrations to be associated cross-sectionally with better LV systolic function and smaller LVESD at baseline. The association persisted after adjusting for several potential confounders, including cardiovascular risk factors and calcium, phosphate, and parathyroid hormone levels. Randomized clinical trials are needed to establish firmly or refute a causal relationship between vitamin D levels and changes in LV geometry and function.

  • 42.
    Fall, Tove
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Xie, Weijia
    Poon, Wenny
    Yaghootkar, Hanieh
    Maegi, Reedik
    Knowles, Joshua W.
    Lyssenko, Valeriya
    Weedon, Michael
    Frayling, Timothy M.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Using Genetic Variants to Assess the Relationship Between Circulating Lipids and Type 2 Diabetes2015In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 64, no 7, p. 2676-2684Article in journal (Refereed)
    Abstract [en]

    The effects of dyslipidemia on the risk of type 2 diabetes (T2D) and related traits are not clear. We used regression models and 140 lipid-associated genetic variants to estimate associations between circulating HDL cholesterol (HDL-C), LDL cholesterol (LDL-C), and triglycerides and T2D and related traits. Each genetic test was corrected for effects of variants on the other two lipid types and surrogates of adiposity. We used the largest data sets available: 34,840 T2D case and 114,981 control subjects from the DIAGRAM (DIAbetes Genetics Replication And Meta-analysis) consortium and up to 133,010 individuals without diabetes for insulin secretion and sensitivity from the MAGIC (Meta-Analyses of Glucose and Insulin-related traits Consortium) and GENESIS (GENEticS of Insulin Sensitivity) studies. Eight of 21 associations between groups of variants and diabetes traits were significant at the nominal level, including those between genetically determined lower HDL-C ( = -0.12, P = 0.03) and T2D and genetically determined lower LDL-C ( = -0.21, P = 5 x 10(-6)) and T2D. Although some of these may represent causal associations, we discuss why caution must be used when using Mendelian randomization in the context of circulating lipid levels and diabetes traits. In conclusion, we found evidence of links between genetic variants associated with lipids and T2D, but deeper knowledge of the underlying genetic mechanisms of specific lipid variants is needed before drawing definite conclusions about causality based on Mendelian randomization methodology.

  • 43.
    Flannick, Jason
    et al.
    Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA USA.;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Fuchsberger, Christian
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI USA..
    Mahajan, Anubha
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    Teslovich, Tanya M.
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI USA..
    Agarwala, Vineeta
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;MIT, Harvard Div Hlth Sci & Technol, Cambridge, MA USA..
    Gaulton, Kyle J.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    Caulkins, Lizz
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Koesterer, Ryan
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Ma, Clement
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI USA..
    Moutsianas, Loukas
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    McCarthy, Davis J.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Dept Stat, Oxford, England..
    Rivas, Manuel A.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    Perry, John R. B.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Exeter, Univ Exeter Med Sch, Genet Complex Traits, Exeter, Devon, England.;Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.;Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Sim, Xueling
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI USA..
    Blackwell, Thomas W.
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI USA..
    Robertson, Neil R.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Rayner, N. William
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambridgeshire, England..
    Cingolani, Pablo
    McGill Univ, Sch Comp Sci, Montreal, PQ, Canada.;McGill Univ, Genome Quebec Innovat Ctr, Montreal, PQ H3A 2T5, Canada..
    Locke, Adam E.
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI USA..
    Tajes, Juan Fernandez
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    Highland, Heather M.
    Univ Texas Grad Sch Biomed Sci, Ctr Human Genet, Univ Texas Hlth Sci Ctr, Houston, TX USA..
    Dupuis, Josee
    Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA USA.;Boston Univ Sch Publ Hlth, Dept Biostatist, Boston, MA USA.;Nat Heart Lung & Blood Inst Framingham Heart Stud, Framingham, MA USA..
    Chines, Peter S.
    NIH, Natl Human Genome Res Inst, Med Genom & Metab Genet Branch, Bethesda, MD USA..
    Lindgren, Cecilia M.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    Hartl, Christopher
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Jackson, Anne U.
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI USA..
    Chen, Han
    Boston Univ Sch Publ Hlth, Dept Biostatist, Boston, MA USA.;Harvard Sch Publ Hlth, Dept Biostatist, Boston, MA USA..
    Huyghe, Jeroen R.
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI USA..
    De Bunt, Martijn Van
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Pearson, Richard D.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    Kumar, Ashish
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Basel, Swiss Trop & Publ Hlth Inst, Chron Dis Epidemiol, Basel, Switzerland..
    Muller-Nurasyid, Martina
    German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Univ Hosp Grosshadern, Ludwig Maximilians Univ, Dept Med I, Munich, Germany.;Ludwig Maximilians Univ Munchen, IBE, Chair Genet Epidemiol, Fac Med, Munich, Germany.;DZHK German Ctr Cardiovascular Res, Munich Heart Alliance, Munich, Germany..
    Grarup, Niels
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Stringham, Heather M.
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI USA..
    Gamazon, Eric R.
    Univ Chicago, Med Genet Sect, Dept Med, Chicago, IL USA..
    Lee, Jaehoon
    Seoul Natl Univ, Dept Stat, Seoul, South Korea..
    Chen, Yuhui
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    Scott, Robert A.
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Below, Jennifer E.
    Univ Texas Hlth Sci Ctr, Sch Publ Hlth, Ctr Human Genet, Houston, TX USA..
    Chen, Peng
    Natl Univ Singapore, Natl Univ Hlth Syst, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Huang, Jinyan
    Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA..
    Go, Min Jin
    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbukdo, South Korea..
    Stitzel, Michael L.
    Jackson Lab Genom Med, Farmington, CT USA..
    Pasko, Dorota
    Univ Exeter, Univ Exeter Med Sch, Genet Complex Traits, Exeter, Devon, England..
    Parker, Stephen C. J.
    Univ Michigan, Dept Computat Med Bioinformat, Ann Arbor, MI USA.;Univ Michigan, Dept Human Genet, Ann Arbor, MI USA..
    Varga, Tibor V.
    Lund Univ, Lund Univ Diabet Ctr, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden..
    Green, Todd
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Beer, Nicola L.
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Day-Williams, Aaron G.
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambridgeshire, England..
    Ferreira, Teresa
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    Fingerlin, Tasha
    Univ Colorado, Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO USA..
    Horikoshi, Momoko
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Hu, Cheng
    Shanghai Jiao Tong Univ, Shanghai Diabet Inst, Dept Endocrinol & Metab, Sixth Peoples Hosp, Shanghai, Peoples R China..
    Huh, Iksoo
    Seoul Natl Univ, Dept Stat, Seoul, South Korea..
    Ikram, Mohammad Kamran
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Singapore, Natl Univ Hlth Syst, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.;Eye Acad Clin Programme, Duke NUS Grad Med Sch, Singapore, Singapore..
    Kim, Bong-Jo
    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbukdo, South Korea..
    Kim, Yongkang
    Seoul Natl Univ, Dept Stat, Seoul, South Korea..
    Kim, Young Jin
    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbukdo, South Korea..
    Kwon, Min-Seok
    Seoul Natl Univ, Interdisciplinary Program Bioinformat, Seoul, South Korea..
    Lee, Juyoung
    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbukdo, South Korea..
    Lee, Selyeong
    Seoul Natl Univ, Dept Stat, Seoul, South Korea..
    Lin, Keng-Han
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI USA..
    Maxwell, Taylor J.
    Univ Texas Hlth Sci Ctr, Sch Publ Hlth, Ctr Human Genet, Houston, TX USA..
    Nagai, Yoshihiko
    McGill Univ, Genome Quebec Innovat Ctr, Montreal, PQ H3A 2T5, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ, Canada.;Res Inst McGill Univ Hlth Ctr, Montreal, PQ, Canada..
    Wang, Xu
    Natl Univ Singapore, Natl Univ Hlth Syst, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Welch, Ryan P.
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI USA..
    Yoon, Joon
    Seoul Natl Univ, Interdisciplinary Program Bioinformat, Seoul, South Korea..
    Zhang, Weihua
    Imperial Coll London, Dept Epidemiol & Biostat, London, England.;Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England..
    Barzilai, Nir
    Albert Einstein Coll Med, Dept Med, New York, NY USA.;Albert Einstein Coll Med, Dept Genet, New York, NY USA..
    Voight, Benjamin F.
    Univ Pennsylvania, Dept Syst Pharmacol & Translat Therapeut, Perelman Sch Med, Philadelphia, PA USA.;Univ Pennsylvania, Dept Genet, Perelman Sch Med, Philadelphia, PA USA..
    Han, Bok-Ghee
    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbukdo, South Korea..
    Jenkinson, Christopher P.
    Univ Texas Hlth Sci Ctr, Dept Med, San Antonio, TX USA.;South Texas Vet Hlth Care Syst, Res, San Antonio, TX USA..
    Kuulasmaa, Teemu
    Univ Eastern Finland, Inst Clin Med, Fac Hlth Sci, Internal Med, Kuopio, Finland..
    Kuusisto, Johanna
    Univ Eastern Finland, Inst Clin Med, Fac Hlth Sci, Internal Med, Kuopio, Finland.;Kuopio Univ Hosp, Kuopio, Finland..
    Manning, Alisa
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Ng, Maggie C. Y.
    Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA..
    Palmer, Nicholette D.
    Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA.;Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA..
    Balkau, Beverley
    Inserm U1018, Ctr Res Epidemiol & Populat Hlth, Villejuif, France..
    Stancakova, Alena
    Univ Eastern Finland, Inst Clin Med, Fac Hlth Sci, Internal Med, Kuopio, Finland..
    Abboud, Hanna E.
    Univ Texas Hlth Sci Ctr, Dept Med, San Antonio, TX USA..
    Boeing, Heiner
    German Inst Human Nutr Potsdam Rehbrucke, Nuthetal, Germany..
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Prabhakaran, Dorairaj
    Ctr Chron Dis Control, New Delhi, India..
    Gottesman, Omri
    Charles Bronfman Inst Personalized Med, Icahn Sch Med, Mt Sinai, New York, NY USA..
    Scott, James
    Natl Heart & Lung Inst, Cardiovascular Sci, Imperial Coll London, Hammersmith Campus, London, England..
    Carey, Jason
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Kwan, Phoenix
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI USA..
    Grant, George
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Smith, Joshua D.
    Univ Washington Sch Med, Dept Genome Sci, Seattle, WA USA..
    Neale, Benjamin M.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA USA..
    Purcell, Shaun
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Dept Med, Ctr Genom Med, Boston, MA USA.;Icahn Inst Genom & Multiscale Biol, Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY USA..
    Butterworth, Adam S.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England..
    Howson, Joanna M. M.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England..
    Lee, Heung Man
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Peoples R China..
    Lu, Yingchang
    Charles Bronfman Inst Personalized Med, Icahn Sch Med, Mt Sinai, New York, NY USA..
    Kwak, Soo-Heon
    Seoul Natl Univ Coll Med, Dept Internal Med, Seoul, South Korea..
    Zhao, Wei
    Univ Pennsylvania, Dept Med, Philadelphia, PA USA..
    Danesh, John
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambridgeshire, England.;Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.;Univ Cambridge, Dept Publ Hlth & Primary Care, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Cambridge, England..
    Lam, Vincent K. L.
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Peoples R China..
    Park, Kyong Soo
    Seoul Natl Univ, Dept Mol Med & Biopharmaceut Sci, Grad Sch Convergence Sci & Technol, Seoul, South Korea.;Seoul Natl Univ, Coll Med, Seoul, South Korea..
    Saleheen, Danish
    Univ Pennsylvania, Dept Biostatist & Epidemiol, Philadelphia, PA USA.;Ctr Non Communicable Dis, Karachi, Pakistan..
    So, Wing Yee
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Peoples R China..
    Tam, Claudia H. T.
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Peoples R China..
    Afzal, Uzma
    Imperial Coll London, Dept Epidemiol & Biostat, London, England..
    Aguilar, David
    Baylor Coll Med, Cardiovascular Div, Houston, TX USA..
    Arya, Rector
    Univ Texas Hlth Sci Ctr, Dept Pediat, San Antonio, TX USA..
    Aung, Tin
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Singapore, Natl Univ Hlth Syst, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.;Eye Acad Clin Programme, Duke NUS Grad Med Sch, Singapore, Singapore..
    Chan, Edmund
    Natl Univ Singapore, Natl Univ Hlth Syst, Yong Loo Lin Sch Med, Dept Med, Singapore, Singapore..
    Navarro, Carmen
    Murcia Reg Hlth Council, Dept Epidemiol, IMIB Arrixaca, Murcia, Spain.;CIBER Epidemiol Salud Publ CIBERESP, Madrid, Spain.;Univ Murcia, Sch Med, Unit Prevent Med & Publ Hlth, Murcia, Spain..
    Cheng, Ching-Yu
    Natl Univ Singapore, Natl Univ Hlth Syst, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Singapore, Natl Univ Hlth Syst, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.;Eye Acad Clin Programme, Duke NUS Grad Med Sch, Singapore, Singapore..
    Palli, Domenico
    Canc Res & Prevent Inst ISPO, Florence, Italy..
    Correa, Adolfo
    Univ Mississippi Med Ctr, Dept Med, Jackson, MS USA..
    Curran, Joanne E.
    Univ Texas Hlth Sci Ctr, San Antonio Univ Texas Rio Grande Valley, Reg Acad Hlth Ctr, South Texas Diabet & Obes Inst, Brownsville, TX USA..
    Rybin, Dennis
    Boston Univ Sch Publ Hlth, Dept Biostatist, Boston, MA USA..
    Farook, Vidya S.
    Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA..
    Fowler, Sharon P.
    Univ Texas Hlth Sci Ctr, Dept Med, San Antonio, TX USA..
    Freedman, Barry I.
    Wake Forest Sch Med, Nephrol Sect, Dept Internal Med, Winston Salem, NC USA..
    Griswold, Michael
    Univ Mississippi, Med Ctr, Ctr Biostat & Bioinformat, Jackson, MS 39216 USA..
    Hale, Daniel Esten
    Univ Texas Hlth Sci Ctr, Dept Pediat, San Antonio, TX USA..
    Hicks, Pamela J.
    Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA.;Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA..
    Khor, Chiea-Chuen
    Natl Univ Singapore, Natl Univ Hlth Syst, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Singapore, Natl Univ Hlth Syst, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.;Natl Univ Singapore, Natl Univ Hlth Syst, Dept Paediat, Yong Loo Lin Sch Med, Singapore, Singapore..
    Kumar, Satish
    Univ Texas Hlth Sci Ctr, San Antonio Univ Texas Rio Grande Valley, Reg Acad Hlth Ctr, South Texas Diabet & Obes Inst, Brownsville, TX USA..
    Lehne, Benjamin
    Imperial Coll London, Dept Epidemiol & Biostat, London, England..
    Thuillier, Dorothee
    Univ Lille, Lille Pasteur Inst, CNRS UMR8199, Lille, France..
    Lim, Wei Yen
    Natl Univ Singapore, Natl Univ Hlth Syst, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Liu, Jianjun
    Natl Univ Singapore, Natl Univ Hlth Syst, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;ASTAR, Genome Inst Singapore, Divis Human Genet, Singapore, Singapore..
    Loh, Marie
    Imperial Coll London, Dept Epidemiol & Biostat, London, England.;Univ Oulu, Inst Hlth Sci, Oulu, Finland.;ASTAR, Translat Lab Genet Med TLGM, Singapore, Singapore..
    Musani, Solomon K.
    Univ Mississippi, Med Ctr, Jackson Heart Study, Jackson, MS 39216 USA..
    Puppala, Sobha
    Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA..
    Scott, William R.
    Imperial Coll London, Dept Epidemiol & Biostat, London, England..
    Yengo, Loic
    Univ Lille, Lille Pasteur Inst, CNRS UMR8199, Lille, France..
    Tan, Sian-Tsung
    Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England.;Natl Heart & Lung Inst, Cardiovascular Sci, Imperial Coll London, Hammersmith Campus, London, England..
    Taylor, Herman A.
    Univ Mississippi Med Ctr, Dept Med, Jackson, MS USA..
    Thameem, Farook
    Univ Texas Hlth Sci Ctr, Dept Med, San Antonio, TX USA..
    Wilson, Gregory
    Jackson State Univ, Coll Publ Serv, Jackson, MS USA..
    Wong, Tien Yin
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Singapore, Natl Univ Hlth Syst, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.;Eye Acad Clin Programme, Duke NUS Grad Med Sch, Singapore, Singapore..
    Njolstad, Pal Rasmus
    Univ Bergen, Dept Clin Sci, KG Jebsen Ctr Diabet Res, Bergen, Norway.;Haukeland Hosp, Dept Pediat, Bergen, Norway..
    Levy, Jonathan C.
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Mangino, Massimo
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England.;Guys & St Thomas Fdn Trust, NIHR Biomed Res Ctr, London, England..
    Bonnycastle, Lori L.
    NIH, Natl Human Genome Res Inst, Med Genom & Metab Genet Branch, Bethesda, MD USA..
    Schwarzmayr, Thomas
    Helmholtz Zentrum Munchen, Inst Human Genet, German Res Ctr Environm Hlth, Neuherberg, Germany..
    Fadista, Joao
    Lund Univ, Dept Clin Sci Diabet & Endocrinol, Ctr Diabet, Malmo, Sweden..
    Surdulescu, Gabriela L.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Herder, Christian
    Heinrich Heine Univ, German Diabet Ctr, Leibniz Ctr Diabet Res, Inst Clin Diabetol, Dusseldorf, Germany.;German Ctr Diabet Res DZD, Munich, Germany..
    Groves, Christopher J.
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Wieland, Thomas
    Helmholtz Zentrum Munchen, Inst Human Genet, German Res Ctr Environm Hlth, Neuherberg, Germany..
    Bork-Jensen, Jette
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Brandslund, Ivan
    Univ Southern Denmark, Inst Reg Hlth Res, Odense, Denmark.;Vejle Hosp, Dept Clin Biochem, Vejle, Denmark..
    Christensen, Cramer
    Vejle Hosp, Dept Internal Med & Endocrinol, Vejle, Denmark..
    Koistinen, Heikki A.
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.;Univ Helsinki, Abdominal Ctr Endocrinol, Helsinki, Finland.;Helsinki Univ Cent Hosp, Abdominal Ctr Endocrinol, Helsinki, Finland.;Minerva Fdn, Helsinki, Finland.;Univ Helsinki, Dept Med, Helsinki, Finland.;Helsinki Univ Cent Hosp, Dept Med, Helsinki, Finland..
    Doney, Alex S. F.
    Med Res Inst, Ninewells Hosp & Med Sch, Divis Cardiovascular & Diabet Med, Dundee, Scotland..
    Kinnunen, Leena
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland..
    Esko, Tonu
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Harvard Med Sch, Dept Genet, Boston, MA USA.;Boston Childrens Hosp, Divis Endocrinol, Boston, MA USA..
    Farmer, Andrew J.
    Univ Oxford, Nuffield Dept Primary Care Hlth Sci, Oxford, England..
    Hakaste, Liisa
    Univ Helsinki, Abdominal Ctr Endocrinol, Helsinki, Finland.;Helsinki Univ Cent Hosp, Abdominal Ctr Endocrinol, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland.;Univ Helsinki, Res Programs Unit, Diabet & Obes, Helsinki, Finland..
    Hodgkiss, Dylan
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Kravic, Jasmina
    Lund Univ, Dept Clin Sci Diabet & Endocrinol, Ctr Diabet, Malmo, Sweden..
    Lyssenko, Valeriya
    Univ Bergen, Dept Clin Sci, KG Jebsen Ctr Diabet Res, Bergen, Norway.;Lund Univ, Dept Clin Sci Diabet & Endocrinol, Ctr Diabet, Malmo, Sweden..
    Hollensted, Mette
    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, Glostrup, Denmark.;Univ Copenhagen, Inst Hlth Sci, Dept Publ Hlth, Copenhagen, Denmark.;Aalborg Univ, Fac Med, Aalborg, Denmark..
    Ladenvall, Claes
    Lund Univ, Dept Clin Sci Diabet & Endocrinol, Ctr Diabet, Malmo, Sweden..
    Justesen, Johanne Marie
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Karajamaki, Annemari
    Vaasa Cent Hosp, Dept Primary Hlth Care, Vaasa, Finland.;Vaasa Hlth Care Ctr, Ctr Diabet, Vaasa, Finland..
    Kriebel, Jennifer
    German Ctr Diabet Res DZD, Munich, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol II, Neuherberg, Germany.;Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Neuherberg, Germany..
    Rathmann, Wolfgang
    German Ctr Diabet Res DZD, Munich, Germany.;Heinrich Heine Univ, German Diabet Ctr, Leibniz Ctr Diabet Res, Inst Biometr & Epidemiol, Dusseldorf, Germany..
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lauritzen, Torsten
    Aarhus Univ, Sect Gen Practice, Dept Publ Hlth, Aarhus, Denmark..
    Narisu, Narisu
    NIH, Natl Human Genome Res Inst, Med Genom & Metab Genet Branch, Bethesda, MD USA..
    Linneberg, Allan
    Capital Region Denmark, Res Ctr Prevent & Hlth, Glostrup, Denmark.;Dept Clin Expt Res, Rigshospitalet, Glostrup, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark..
    Melander, Olle
    Lund Univ, Dept Clin Sci, Hypertens & Cardiovascular Dis, Malmo, Sweden..
    Milani, Lili
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Neville, Matt
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    Orho-Melander, Marju
    Lund Univ, Dept Clin Sci, Diabet & Cardiovascular Dis, Genet Epidemiol, Malmo, Sweden..
    Qi, Lu
    Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Brigham & Womens Hosp & Harvard Med Sch, Channing Div Network Med, Dept Med, Boston, MA USA..
    Qi, Qibin
    Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA..
    Roden, Michael
    Heinrich Heine Univ, German Diabet Ctr, Leibniz Ctr Diabet Res, Inst Clin Diabetol, Dusseldorf, Germany.;German Ctr Diabet Res DZD, Munich, Germany.;Heinrich Heine Univ, Fac Med, Divis Endocrinol & Diabetol, Dusseldorf, Germany..
    Rolandsson, Olov
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Swift, Amy
    NIH, Natl Human Genome Res Inst, Med Genom & Metab Genet Branch, Bethesda, MD USA..
    Rosengren, Anders H.
    Lund Univ, Dept Clin Sci Diabet & Endocrinol, Ctr Diabet, Malmo, Sweden..
    Stirrups, Kathleen
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambridgeshire, England..
    Wood, Andrew R.
    Univ Exeter, Univ Exeter Med Sch, Genet Complex Traits, Exeter, Devon, England..
    Mihailov, Evelin
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Blancher, Christine
    Univ Oxford, Nuffield Dept Med, Oxford Genom Ctr, Wellcome Trust Ctr Human Genet, Oxford, England..
    Carneiro, Mauricio O.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Maguire, Jared
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Poplin, Ryan
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Shakir, Khalid
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Fennell, Timothy
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    DePristo, Mark
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    De Angelis, Martin Hrabe
    German Ctr Diabet Res DZD, Munich, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Expt Genet, Neuherberg, Germany.;Tech Univ Munich, Ctr Life & Food Sci Weihenstephan, Freising Weihenstephan, Germany..
    Deloukas, Panos
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambridgeshire, England.;Queen Mary Univ London, William Harvey Res Inst, London, England.;Queen Mary Univ London, London Sch Med & Dent, London, England.;King Abdulaziz Univ, Princess Jawhara Brahim Ctr Excellence Res Heredi, Jeddah, Saudi Arabia..
    Gjesing, Anette P.
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Jun, Goo
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI USA.;Univ Texas Hlth Sci Ctr, Sch Publ Hlth, Ctr Human Genet, Houston, TX USA..
    Nilsson, Peter M.
    Lund Univ, Dept Clin Sci, Malmo, Sweden.;Lund Univ, Dept Med, Malmo, Sweden..
    Murphy, Jacquelyn
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Onofrio, Robert
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Thorand, Barbara
    German Ctr Diabet Res DZD, Munich, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol II, Neuherberg, Germany..
    Hansen, Torben
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark.;Univ Southern Denmark, Fac Hlth Sci, Odense, Denmark..
    Meisinger, Christa
    German Ctr Diabet Res DZD, Munich, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol II, Neuherberg, Germany..
    Hu, Frank B.
    Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.;Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA..
    Isomaa, Bo
    Folkhalsan Res Ctr, Helsinki, Finland.;Dept Social Serv & Hlth Care, Pietarsaari, Finland..
    Karpe, Fredrik
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    Liang, Liming
    Harvard Sch Publ Hlth, Dept Biostatist, Boston, MA USA.;Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA..
    Peters, Annette
    DZHK German Ctr Cardiovascular Res, Munich Heart Alliance, Munich, Germany.;German Ctr Diabet Res DZD, Munich, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol II, Neuherberg, Germany..
    Huth, Cornelia
    German Ctr Diabet Res DZD, Munich, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol II, Neuherberg, Germany..
    O'Rahilly, Stephen P.
    Univ Cambridge, Inst Metab Sci, Metabol Res Labs, Cambridge, England..
    Palmer, Colin N. A.
    Ninewells Hosp & Med Sch, Pat Macpherson Ctr Pharmacogenet & Pharmacogenet, Dundee, Scotland.;Ninewells Hosp & Med Sch, Med Res Inst, Dundee, Scotland..
    Pedersen, Oluf
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Rauramaa, Rainer
    Kuopio Res Inst Exercise Med, Foundat Res Hlth Exercise & Nutr, Kuopio, Finland..
    Tuomilehto, Jaakko
    Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria.;King Abdulaziz Univ, Diabetes Res Grp, Jeddah, Saudi Arabia.;Dasman Diabet Inst, Kuwait, Kuwait.;Natl Inst Hlth & Welf, Helsinki, Finland..
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Helsinki, Finland..
    Watanabe, Richard M.
    Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA.;Univ Southern Calif, Keck Sch Med, Dept Physiol Biophys, Los Angeles, CA USA.;Univ Southern Calif, Diabet & Obes Res Inst, Keck Sch Med, Los Angeles, CA USA..
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bergman, Richard N.
    Cedars Sinai Diabet & Obes Res Inst, Los Angeles, CA USA..
    Bharadwaj, Dwaipayan
    CSIR Inst Genom Integrat Biol CSIR IGIB, Funct Genom Unit, New Delhi, India..
    Bottinger, Erwin P.
    Charles Bronfman Inst Personalized Med, Icahn Sch Med, Mt Sinai, New York, NY USA..
    Cho, Yoon Shin
    Hallym Univ, Dept Biomed Sci, Chunchon, South Korea..
    Chandak, Giriraj R.
    CSIR, Ctr Cellular & Mol Biol, Hyderabad, Andhra Pradesh, India..
    Chan, Juliana Cn
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Hong Kong Inst Diabet & Obes, Hong Kong, Peoples R China..
    Chia, Kee Seng
    Natl Univ Singapore, Natl Univ Hlth Syst, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Daly, Mark J.
    Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA USA..
    Ebrahim, Shah B.
    Ctr Chron Dis Control, New Delhi, India..
    Langenberg, Claudia
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Elliott, Paul
    Imperial Coll London, Dept Epidemiol & Biostat, London, England.;Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England..
    Jablonski, Kathleen A.
    George Washington Univ, Biostatist Ctr, Rockville, MD USA..
    Lehman, Donna M.
    Univ Texas Hlth Sci Ctr, Dept Med, San Antonio, TX USA..
    Jia, Weiping
    Shanghai Jiao Tong Univ, Shanghai Diabet Inst, Dept Endocrinol & Metab, Sixth Peoples Hosp, Shanghai, Peoples R China..
    Ma, Ronald Cw
    Boston Univ Sch Publ Hlth, Dept Biostatist, Boston, MA USA.;Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Hong Kong Inst Diabet & Obes, Hong Kong, Peoples R China..
    Pollin, Toni I.
    Univ Maryland Sch Med, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD USA.;Univ Maryland Sch Med, Program Personalized Genom Med, Baltimore, MD USA..
    Sandhu, Manjinder
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambridgeshire, England.;Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England..
    Tandon, Nikhil
    All India Inst Med Sci, Dept Endocrinol & Metab, New Delhi, India..
    Froguel, Philippe
    Univ Lille, Lille Pasteur Inst, CNRS UMR8199, Lille, France.;Imperial Coll London, Sch Publ Hlth, Dept Genom Common Dis, London, England..
    Barroso, Ines
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambridgeshire, England.;Univ Cambridge, Inst Metab Sci, Metabol Res Labs, Cambridge, England..
    Teo, Yik Ying
    Natl Univ Singapore, Natl Univ Hlth Syst, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Natl Univ Singapore, Inst Life Sci, Singapore, Singapore.;Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore, Singapore..
    Zeggini, Eleftheria
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambridgeshire, England..
    Loos, Ruth J. F.
    Charles Bronfman Inst Personalized Med, Icahn Sch Med, Mt Sinai, New York, NY USA..
    Small, Kerrin S.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Ried, Janina S.
    German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany..
    DeFronzo, Ralph A.
    Univ Texas Hlth Sci Ctr, Dept Med, San Antonio, TX USA..
    Grallert, Harald
    German Ctr Diabet Res DZD, Munich, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol II, Neuherberg, Germany.;Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Neuherberg, Germany..
    Glaser, Benjamin
    Hadassah Hebrew Univ Med Ctr, Endocrinol & Metab Serv, Jerusalem, Israel..
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Wareham, Nicholas J.
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Walker, Mark
    Newcastle Univ, Inst Cellular Med, Sch Med, Newcastle Upon Tyne, Tyne & Wear, England..
    Banks, Eric
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Gieger, Christian
    German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol II, Neuherberg, Germany.;Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Neuherberg, Germany..
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.
    Im, Hae Kyung
    Univ Chicago, Med Genet Sect, Dept Med, Chicago, IL USA..
    Illig, Thomas
    Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Neuherberg, Germany.;Hannover Med Sch, Hannover Unified Biobank, Hannover, NH, Germany.;Hannover Med Sch, Dept Human Genet, Hannover, NH, Germany..
    Franks, Paul W.
    Lund Univ, Lund Univ Diabet Ctr, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden.;Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Buck, Gemma
    Univ Oxford, Nuffield Dept Med, Oxford Genom Ctr, Wellcome Trust Ctr Human Genet, Oxford, England..
    Trakalo, Joseph
    Univ Oxford, Nuffield Dept Med, Oxford Genom Ctr, Wellcome Trust Ctr Human Genet, Oxford, England..
    Buck, David
    Univ Oxford, Nuffield Dept Med, Oxford Genom Ctr, Wellcome Trust Ctr Human Genet, Oxford, England..
    Prokopenko, Inga
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Imperial Coll London, Sch Publ Hlth, Dept Genom Common Dis, London, England..
    Magi, Reedik
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Farjoun, Yossi
    Broad Inst, Data Sci & Data Engn, Cambridge, MA USA..
    Owen, Katharine R.
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    Gloyn, Anna L.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    Strauch, Konstantin
    German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Ludwig Maximilians Univ Munchen, IBE, Chair Genet Epidemiol, Fac Med, Munich, Germany..
    Tuomi, Tiinamaija
    Univ Helsinki, Abdominal Ctr Endocrinol, Helsinki, Finland.;Helsinki Univ Cent Hosp, Abdominal Ctr Endocrinol, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland.;Univ Helsinki, Res Programs Unit, Diabet & Obes, Helsinki, Finland.;Univ Helsinki, Finnish Inst Mol Med, Helsinki, Finland..
    Kooner, Jaspal Singh
    Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England.;Natl Heart & Lung Inst, Cardiovascular Sci, Imperial Coll London, Hammersmith Campus, London, England.;Imperial Coll London, Imperial Coll Healthcare NHS Trust, London, England..
    Lee, Jong-Young
    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbukdo, South Korea..
    Park, Taesung
    Seoul Natl Univ, Dept Stat, Seoul, South Korea.;Seoul Natl Univ, Interdisciplinary Program Bioinformat, Seoul, South Korea..
    Donnelly, Peter
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Dept Stat, Oxford, England..
    Morris, Andrew D.
    Ninewells Hosp & Med Sch, Ctr Mol Med, Clin Res Ctr, Dundee, Scotland.;Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland..
    Hattersley, Andrew T.
    Univ Exeter, Univ Exeter Med Sch, Exeter, Devon, England..
    Bowden, Donald W.
    Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA.;Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA..
    Collins, Francis S.
    NIH, Natl Human Genome Res Inst, Med Genom & Metab Genet Branch, Bethesda, MD USA..
    Atzmon, Gil
    Albert Einstein Coll Med, Dept Med, New York, NY USA.;Albert Einstein Coll Med, Dept Genet, New York, NY USA.;Univ Haifa, Dept Nat Sci, Haifa, Israel..
    Chambers, John C.
    Imperial Coll London, Dept Epidemiol & Biostat, London, England.;Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England.;Imperial Coll London, Imperial Coll Healthcare NHS Trust, London, England..
    Spector, Timothy D.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Laakso, Markku
    Univ Eastern Finland, Inst Clin Med, Fac Hlth Sci, Internal Med, Kuopio, Finland.;Kuopio Univ Hosp, Kuopio, Finland..
    Strom, Tim M.
    Helmholtz Zentrum Munchen, Inst Human Genet, German Res Ctr Environm Hlth, Neuherberg, Germany.;Tech Univ Munich, Inst Human Genet, Munich, Germany..
    Bell, Graeme I.
    Univ Chicago, Dept Med, Chicago, IL USA.;Univ Chicago, Dept Human Genet, Chicago, IL USA..
    Blangero, John
    Univ Texas Hlth Sci Ctr, San Antonio Univ Texas Rio Grande Valley, Reg Acad Hlth Ctr, South Texas Diabet & Obes Inst, Brownsville, TX USA..
    Duggirala, Ravindranath
    Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA..
    Tai, EShyong
    Natl Univ Singapore, Natl Univ Hlth Syst, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Natl Univ Singapore, Natl Univ Hlth Syst, Yong Loo Lin Sch Med, Dept Med, Singapore, Singapore.;Duke NUS Med Sch Singapore, Cardiovascular Metab Disorders Program, Singapore, Singapore..
    McVean, Gilean
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Li Ka Shing Ctr Hlth Informat & Discovery, Oxford, England..
    Hanis, Craig L.
    Univ Texas Hlth Sci Ctr, Sch Publ Hlth, Ctr Human Genet, Houston, TX USA..
    Wilson, James G.
    Univ Mississippi Med Ctr, Dept Physiol & Biophys, Jackson, MS USA..
    Seielstad, Mark
    Univ Calif San Francisco, Dept Lab Med, Inst Human Genet, San Francisco, CA USA.;Blood Syst Res Inst, San Francisco, CA USA..
    Frayling, Timothy M.
    Univ Exeter, Univ Exeter Med Sch, Genet Complex Traits, Exeter, Devon, England..
    Meigs, James B.
    Harvard Med Sch, Massachusetts Gen Hosp, Div Gen Med, Boston, MA USA.;Harvard Med Sch, Dept Med, Boston, MA USA..
    Cox, Nancy J.
    Univ Chicago, Med Genet Sect, Dept Med, Chicago, IL USA..
    Sladek, Rob
    McGill Univ, Genome Quebec Innovat Ctr, Montreal, PQ H3A 2T5, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ, Canada.;McGill Univ, Dept Med, Divis Endocrinol & Metab, Montreal, PQ, Canada..
    Lander, Eric S.
    MIT, Broad Inst, Cambridge, MA USA..
    Gabriel, Stacey
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Mohlke, Karen L.
    Univ N Carolina, Dept Genet, Chapel Hill, NC USA..
    Meitinger, Thomas
    Helmholtz Zentrum Munchen, Inst Human Genet, German Res Ctr Environm Hlth, Neuherberg, Germany.;Tech Univ Munich, Inst Human Genet, Munich, Germany..
    Groop, Leif
    Lund Univ, Dept Clin Sci Diabet & Endocrinol, Ctr Diabet, Malmo, Sweden.;Univ Helsinki, Finnish Inst Mol Med, Helsinki, Finland..
    Abecasis, Goncalo
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI USA..
    Scott, Laura J.
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI USA..
    Morris, Andrew P.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England..
    Kang, Hyun Min
    Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA USA..
    Altshuler, David
    Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA USA.;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Harvard Med Sch, Dept Genet, Boston, MA USA.;Harvard Med Sch, Dept Med, Boston, MA USA.;Massachusetts Gen Hosp, Dept Med, Diabet Res Ctr Diabet Unit, Boston, MA USA.;MIT, Dept Biol, Cambridge, MA 02139 USA..
    Burtt, Noel P.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Florez, Jose C.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Dept Med, Ctr Genom Med, Boston, MA USA.;Harvard Med Sch, Dept Med, Boston, MA USA.;Massachusetts Gen Hosp, Dept Med, Diabet Res Ctr Diabet Unit, Boston, MA USA..
    Boehnke, Michael
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI USA..
    McCarthy, Mark I.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    Data Descriptor: Sequence data and association statistics from 12,940 type 2 diabetes cases and controls2017In: Scientific Data, E-ISSN 2052-4463, Vol. 4, article id 170179Article in journal (Refereed)
    Abstract [en]

    To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.

  • 44. Flannick, Jason
    et al.
    Thorleifsson, Gudmar
    Beer, Nicola L.
    Jacobs, Suzanne B. R.
    Grarup, Niels
    Burtt, Noel P.
    Mahajan, Anubha
    Fuchsberger, Christian
    Atzmon, Gil
    Benediktsson, Rafn
    Blangero, John
    Bowden, Don W.
    Brandslund, Ivan
    Brosnan, Julia
    Burslem, Frank
    Chambers, John
    Cho, Yoon Shin
    Christensen, Cramer
    Douglas, Desiree A.
    Duggirala, Ravindranath
    Dymek, Zachary
    Farjoun, Yossi
    Fennell, Timothy
    Fontanillas, Pierre
    Forsen, Tom
    Gabriel, Stacey
    Glaser, Benjamin
    Gudbjartsson, Daniel F.
    Hanis, Craig
    Hansen, Torben
    Hreidarsson, Astradur B.
    Hveem, Kristian
    Ingelsson, Erik
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Isomaa, Bo
    Johansson, Stefan
    Jorgensen, Torben
    Jorgensen, Marit Eika
    Kathiresan, Sekar
    Kong, Augustine
    Kooner, Jaspal
    Kravic, Jasmina
    Laakso, Markku
    Lee, Jong-Young
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lindgren, Cecilia M.
    Linneberg, Allan
    Masson, Gisli
    Meitinger, Thomas
    Mohlke, Karen L.
    Molven, Anders
    Morris, Andrew P.
    Potluri, Shobha
    Rauramaa, Rainer
    Ribel-Madsen, Rasmus
    Richard, Ann-Marie
    Rolph, Tim
    Salomaa, Veikko
    Segre, Ayellet V.
    Skaerstrand, Hanna
    Steinthorsdottir, Valgerdur
    Stringham, Heather M.
    Sulem, Patrick
    Tai, E. Shyong
    Teo, Yik Ying
    Teslovich, Tanya
    Thorsteinsdottir, Unnur
    Trimmer, Jeff K.
    Tuomi, Tiinamaija
    Tuomilehto, Jaakko
    Vaziri-Sani, Fariba
    Voight, Benjamin F.
    Wilson, James G.
    Boehnke, Michael
    McCarthy, Mark I.
    Njolstad, Pal R.
    Pedersen, Oluf
    Groop, Leif
    Cox, David R.
    Stefansson, Kari
    Altshuler, David
    Loss-of-function mutations in SLC30A8 protect against type 2 diabetes2014In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 46, no 4, p. 357-+Article in journal (Refereed)
    Abstract [en]

    Loss-of-function mutations protective against human disease provide in vivo validation of therapeutic targets1-3, but none have yet been described for type 2 diabetes (T2D). Through sequencing or genotyping of -150,000 individuals across 5 ancestry groups, we identified 12 rare protein-truncating variants in SLC30A8, which encodes an islet zinc transporter (ZnT8) 4 and harbors a common variant (p. Trp325Arg) associated with T2D risk and glucose and proinsulin levels5-7. Collectively, carriers of protein-truncating variants had 65% reduced T2D risk (P = 1.7 x 10(-6)), and non-diabetic Icelandic carriers of a frameshift variant (p. Lys34Serfs* 50) demonstrated reduced glucose levels (-0.17 s. d., P = 4.6 x 10(-4)). The two most common proteintruncating variants (p. Arg138* and p. Lys34Serfs* 50) individually associate with T2D protection and encode unstable ZnT8 proteins. Previous functional study of SLC30A8 suggested that reduced zinc transport increases T2D risk(8,9), and phenotypic heterogeneity was observed in mouse Slc30a8 knockouts(10-15). In contrast, loss-of-function mutations in humans provide strong evidence that SLC30A8 haploinsufficiency protects against T2D, suggesting ZnT8 inhibition as a therapeutic strategy in T2D prevention.

  • 45. Folkersen, Lasse
    et al.
    Fauman, Eric
    Sabater-Lleal, Maria
    Strawbridge, Rona J
    Frånberg, Mattias
    Sennblad, Bengt
    Baldassarre, Damiano
    Veglia, Fabrizio
    Humphries, Steve E
    Rauramaa, Rainer
    de Faire, Ulf
    Smit, Andries J
    Giral, Philippe
    Kurl, Sudhir
    Mannarino, Elmo
    Enroth, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Johansson, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bosdotter Enroth, Sofia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lind, Lars
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Lindgren, Cecilia
    Morris, Andrew P
    Giedraitis, Vilmantas
    Silveira, Angela
    Franco-Cereceda, Anders
    Tremoli, Elena
    Gyllensten, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Brunak, Søren
    Eriksson, Per
    Ziemek, Daniel
    Hamsten, Anders
    Mälarstig, Anders
    Mapping of 79 loci for 83 plasma protein biomarkers in cardiovascular disease2017In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 13, no 4, article id e1006706Article in journal (Refereed)
    Abstract [en]

    Recent advances in highly multiplexed immunoassays have allowed systematic large-scale measurement of hundreds of plasma proteins in large cohort studies. In combination with genotyping, such studies offer the prospect to 1) identify mechanisms involved with regulation of protein expression in plasma, and 2) determine whether the plasma proteins are likely to be causally implicated in disease. We report here the results of genome-wide association (GWA) studies of 83 proteins considered relevant to cardiovascular disease (CVD), measured in 3,394 individuals with multiple CVD risk factors. We identified 79 genome-wide significant (p<5e-8) association signals, 55 of which replicated at P<0.0007 in separate validation studies (n = 2,639 individuals). Using automated text mining, manual curation, and network-based methods incorporating information on expression quantitative trait loci (eQTL), we propose plausible causal mechanisms for 25 trans-acting loci, including a potential post-translational regulation of stem cell factor by matrix metalloproteinase 9 and receptor-ligand pairs such as RANK-RANK ligand. Using public GWA study data, we further evaluate all 79 loci for their causal effect on coronary artery disease, and highlight several potentially causal associations. Overall, a majority of the plasma proteins studied showed evidence of regulation at the genetic level. Our results enable future studies of the causal architecture of human disease, which in turn should aid discovery of new drug targets.

  • 46.
    Forsberg, Lars A.
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Rasi, Chiara
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Malmqvist, Niklas
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Davies, Hanna
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Pasupulati, Saichand
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Pakalapati, Geeta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sandgren, Johanna
    de Stahl, Teresita Diaz
    Zaghlool, Ammar
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics.
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Score, Joannah
    Cross, Nicholas C. P.
    Absher, Devin
    Tiensuu Janson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Lindgren, Cecilia M.
    Morris, Andrew P.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Dumanski, Jan P.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Mosaic loss of chromosome Y in peripheral blood is associated with shorter survival and higher risk of cancer2014In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 46, no 6, p. 624-628Article in journal (Refereed)
    Abstract [en]

    Incidence and mortality for sex-unspecific cancers are higher among men, a fact that is largely unexplained(1,2). Furthermore, age-related loss of chromosome Y (LOY) is frequent in normal hematopoietic cells(3,4), but the phenotypic consequences of LOY have been elusive(5-10). From analysis of 1,153 elderly men, we report that LOY in peripheral blood was associated with risks of all-cause mortality (hazards ratio (HR) = 1.91, 95% confidence interval (CI) = 1.17-3.13; 637 events) and non-hematological cancer mortality (HR = 3.62, 95% CI = 1.56-8.41; 132 events). LOY affected at least 8.2% of the subjects in this cohort, and median survival times among men with LOY were 5.5 years shorter. Association of LOY with risk of all-cause mortality was validated in an independent cohort (HR = 3.66) in which 20.5% of subjects showed LOY. These results illustrate the impact of post-zygotic mosaicism on disease risk, could explain why males are more frequently affected by cancer and suggest that chromosome Y is important in processes beyond sex determination. LOY in blood could become a predictive biomarker of male carcinogenesis.

  • 47.
    Fuchsberger, Christian
    et al.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, Innsbruck, Austria.;Univ Lubeck, European Acad Bolzano Bozen EURAC, Ctr Biomed, Bolzano, Italy..
    Flannick, Jason
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA..
    Teslovich, Tanya M.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    Agarwala, Vineeta
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA..
    Gaulton, Kyle J.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    Ma, Clement
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Fontanillas, Pierre
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Moutsianas, Loukas
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    McCarthy, Davis J.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Oxford, Dept Stat, Oxford, England..
    Rivas, Manuel A.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    Perry, John R. B.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Exeter, Sch Med, Genet Complex Traits, Exeter, Devon, England.;Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.;Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Sim, Xueling
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Blackwell, Thomas W.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Robertson, Neil R.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Rayner, N. William
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambs, England..
    Cingolani, Pablo
    McGill Univ, Sch Comp Sci, Montreal, PQ, Canada.;McGill Univ, Montreal, PQ, Canada.;Genome Quebec Innovat Ctr, Montreal, PQ, Canada..
    Locke, Adam E.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Tajes, Juan Fernandez
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    Highland, Heather M.
    Univ Texas Hlth Sci Ctr Houston, Univ Texas Grad Sch Biomed Sci Houston, Human Genet Ctr, Houston, TX 77030 USA..
    Dupuis, Josee
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.;NHLBI, Framingham Heart Study, Framingham, MA USA..
    Chines, Peter S.
    NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA..
    Lindgren, Cecilia M.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    Hartl, Christopher
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Jackson, Anne U.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Chen, Han
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.;Harvard Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Huyghe, Jeroen R.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    van de Bunt, Martijn
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Pearson, Richard D.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    Kumar, Ashish
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Basel, Swiss Trop & Publ Hlth Inst, Chron Dis Epidemiol, Basel, Switzerland..
    Mueller-Nurasyid, Martina
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany.;Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany.;Univ Munich, Chair Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany.;Munich Heart Alliance, DZHK German Ctr Cardiovasc Res, Munich, Germany..
    Grarup, Niels
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Stringham, Heather M.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Gamazon, Eric R.
    Univ Chicago, Dept Med, Med Genet Sect, 5841 S Maryland Ave, Chicago, IL 60637 USA..
    Lee, Jaehoon
    Seoul Natl Univ, Dept Stat, Seoul, South Korea..
    Chen, Yuhui
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    Scott, Robert A.
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Below, Jennifer E.
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX 77030 USA..
    Chen, Peng
    Natl Univ Hlth Syst, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Huang, Jinyan
    Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA..
    Go, Min Jin
    Korea Natl Inst Hlth, Ctr Genome Sci, Cheongju, Chungcheongbuk, South Korea..
    Stitzel, Michael L.
    Jackson Lab Genom Med, Farmington, CT USA..
    Pasko, Dorota
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter, Devon, England..
    Parker, Stephen C. J.
    Univ Michigan, Dept Computat Med, Ann Arbor, MI USA.;Univ Michigan, Dept Bioinformat & Human Genet, Ann Arbor, MI USA..
    Varga, Tibor V.
    Lund Univ, Genet & Mol Epidemiol Unit, Lund Univ Diabet Ctr, Dept Clin Sci, Malmo, Sweden..
    Green, Todd
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Beer, Nicola L.
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Day-Williams, Aaron G.
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambs, England..
    Ferreira, Teresa
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England..
    Fingerlin, Tasha
    Univ Colorado, Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO USA..
    Horikoshi, Momoko
    Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Hu, Cheng
    Shanghai Jiao Tong Univ, Peoples Hosp 6, Shanghai Diabet Inst, Dept Endocrinol & Metab, Shanghai, Peoples R China..
    Huh, Iksoo
    Seoul Natl Univ, Dept Stat, Seoul, South Korea..
    Ikram, Mohammad Kamran
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Hlth Syst, Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.;Duke NUS Grad Med Sch, Eye Acad Clin Programme, Singapore, Singapore..
    Kim, Bong-Jo
    Korea Natl Inst Hlth, Ctr Genome Sci, Cheongju, Chungcheongbuk, South Korea..
    Kim, Yongkang
    Seoul Natl Univ, Dept Stat, Seoul, South Korea..
    Kim, Young Jin
    Korea Natl Inst Hlth, Ctr Genome Sci, Cheongju, Chungcheongbuk, South Korea..
    Kwon, Min-Seok
    Seoul Natl Univ, Interdisciplinary Program Bioinformat, Seoul, South Korea..
    Lee, Juyoung
    Korea Natl Inst Hlth, Ctr Genome Sci, Cheongju, Chungcheongbuk, South Korea..
    Lee, Selyeong
    Seoul Natl Univ, Dept Stat, Seoul, South Korea..
    Lin, Keng-Han
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Maxwell, Taylor J.
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX 77030 USA..
    Nagai, Yoshihiko
    McGill Univ, Montreal, PQ, Canada.;Genome Quebec Innovat Ctr, Montreal, PQ, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ, Canada.;McGill Univ Hlth Ctr, Res Inst, Montreal, PQ, Canada..
    Wang, Xu
    Natl Univ Hlth Syst, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Welch, Ryan P.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Yoon, Joon
    Seoul Natl Univ, Interdisciplinary Program Bioinformat, Seoul, South Korea..
    Zhang, Weihua
    Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England.;Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England..
    Barzilai, Nir
    Albert Einstein Coll Med, Dept Med, New York, NY USA.;Albert Einstein Coll Med, Dept Genet, New York, NY USA..
    Voight, Benjamin F.
    Univ Penn, Perelman Sch Med, Dept Syst Pharmacol & Translat Therapeut, Philadelphia, PA 19104 USA.;Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA..
    Han, Bok-Ghee
    Korea Natl Inst Hlth, Ctr Genome Sci, Cheongju, Chungcheongbuk, South Korea..
    Jenkinson, Christopher P.
    Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.;South Texas Vet Hlth Care Syst, Res, San Antonio, TX USA..
    Kuulasmaa, Teemu
    Univ Eastern Finland, Internal Med, Inst Clin Med, Fac Hlth Sci, Kuopio, Finland..
    Kuusisto, Johanna
    Univ Eastern Finland, Internal Med, Inst Clin Med, Fac Hlth Sci, Kuopio, Finland.;Kuopio Univ Hosp, Kuopio, Finland..
    Manning, Alisa
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Ng, Maggie C. Y.
    Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA..
    Palmer, Nicholette D.
    Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA.;Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA..
    Balkau, Beverley
    INSERM, Ctr Res Epidemiol & Populat Hlth, U1018, Villejuif, France..
    Stancakova, Alena
    Univ Eastern Finland, Internal Med, Inst Clin Med, Fac Hlth Sci, Kuopio, Finland..
    Abboud, Hanna E.
    Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA..
    Boeing, Heiner
    German Inst Human Nutr Potsdam Rehbrucke, Nuthetal, Germany..
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Prabhakaran, Dorairaj
    Ctr Chron Dis Control, New Delhi, India..
    Gottesman, Omri
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Scott, James
    Univ London Imperial Coll Sci Technol & Med, Cardiovasc Sci, Natl Heart & Lung Inst, Hammersmith Campus, London, England..
    Carey, Jason
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Kwan, Phoenix
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA..
    Grant, George
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Smith, Joshua D.
    Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA USA..
    Neale, Benjamin M.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA..
    Purcell, Shaun
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA.;Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Psychiat, New York, NY 10029 USA..
    Butterworth, Adam S.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England..
    Howson, Joanna M. M.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England..
    Lee, Heung Man
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China..
    Lu, Yingchang
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Kwak, Soo-Heon
    Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul, South Korea..
    Zhao, Wei
    Univ Penn, Dept Med, Philadelphia, PA 19104 USA..
    Danesh, John
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambs, England.;Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.;Univ Cambridge, Dept Publ Hlth & Primary Care, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Cambridge, England..
    Lam, Vincent K. L.
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China..
    Park, Kyong Soo
    Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul, South Korea.;Seoul Natl Univ, Grad Sch Convergence Sci & Technol, Dept Mol Med & Biopharmaceut Sci, Seoul, South Korea.;Seoul Natl Univ, Coll Med, Seoul, South Korea..
    Saleheen, Danish
    Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.;Ctr Noncommunicable Dis, Karachi, Pakistan..
    So, Wing Yee
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China..
    Tam, Claudia H. T.
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China..
    Afzal, Uzma
    Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England..
    Aguilar, David
    Baylor Coll Med, Div Cardiovasc, Houston, TX 77030 USA..
    Arya, Rector
    Univ Texas Hlth Sci Ctr San Antonio, Dept Pediat, San Antonio, TX 78229 USA..
    Aung, Tin
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Hlth Syst, Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.;Duke NUS Grad Med Sch, Eye Acad Clin Programme, Singapore, Singapore..
    Chan, Edmund
    Natl Univ Singapore, Natl Univ Hlth Syst, Yong Loo Lin Sch Med, Dept Med, Singapore, Singapore..
    Navarro, Carmen
    IMIB Arrixaca, Murcia Reg Hlth Council, Dept Epidemiol, Murcia, Spain.;Univ Murcia, CIBERESP, Murcia, Spain.;Univ Murcia, Sch Med, Unit Prevent Med & Publ Hlth, E-30001 Murcia, Spain..
    Cheng, Ching-Yu
    Natl Univ Hlth Syst, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Hlth Syst, Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.;Duke NUS Grad Med Sch, Eye Acad Clin Programme, Singapore, Singapore..
    Palli, Domenico
    Canc Res & Prevent Inst ISPO, Florence, Italy..
    Correa, Adolfo
    Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA..
    Curran, Joanne E.
    Univ Texas Rio Grande Valley, Reg Acad Hlth Ctr, South Texas Diabet & Obes Inst, Brownsville, TX USA..
    Rybin, Denis
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Farook, Vidya S.
    Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA..
    Fowler, Sharon P.
    Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA..
    Freedman, Barry I.
    Wake Forest Sch Med, Nephrol Sect, Dept Internal Med, Winston Salem, NC USA..
    Griswold, Michael
    Univ Mississippi, Med Ctr, Ctr Biostat & Bioinformat, Jackson, MS 39216 USA..
    Hale, Daniel Esten
    Univ Texas Hlth Sci Ctr San Antonio, Dept Pediat, San Antonio, TX 78229 USA..
    Hicks, Pamela J.
    Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA.;Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA..
    Khor, Chiea-Chuen
    Natl Univ Hlth Syst, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Hlth Syst, Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.;Natl Univ Singapore, Natl Univ Hlth Syst, Yong Loo Lin Sch Med, Dept Paediat, Singapore, Singapore.;ASTAR, Genome Inst Singapore, Div Human Genet, Singapore, Singapore..
    Kumar, Satish
    Univ Texas Rio Grande Valley, Reg Acad Hlth Ctr, South Texas Diabet & Obes Inst, Brownsville, TX USA..
    Lehne, Benjamin
    Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England..
    Thuillier, Dorothee
    Univ Lille, Lille Pasteur Inst, CNRS UMR8199, Lille, France..
    Lim, Wei Yen
    Natl Univ Hlth Syst, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Liu, Jianjun
    Natl Univ Hlth Syst, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;ASTAR, Genome Inst Singapore, Div Human Genet, Singapore, Singapore..
    van der Schouw, Yvonne T.
    Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands..
    Loh, Marie
    Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England.;Univ Oulu, Inst Hlth Sci, Oulu, Finland.;ASTAR, TLGM, Singapore, Singapore..
    Musani, Solomon K.
    Univ Mississippi, Med Ctr, Jackson Heart Study, Jackson, MS 39216 USA..
    Puppala, Sobha
    Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA..
    Scott, William R.
    Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England..
    Yengo, Loic
    Univ Lille, Lille Pasteur Inst, CNRS UMR8199, Lille, France..
    Tan, Sian-Tsung
    Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England.;Univ London Imperial Coll Sci Technol & Med, Cardiovasc Sci, Natl Heart & Lung Inst, Hammersmith Campus, London, England..
    Taylor, Herman A., Jr.
    Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA..
    Thameem, Farook
    Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA..
    Wilson, Gregory, Sr.
    Jackson State Univ, Coll Publ Serv, Jackson, MS USA..
    Wong, Tien Yin
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Hlth Syst, Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.;Duke NUS Grad Med Sch, Eye Acad Clin Programme, Singapore, Singapore..
    Njolstad, Pal Rasmus
    Univ Bergen, Dept Clin Sci, KG Jebsen Ctr Diabet Res, Bergen, Norway.;Haukeland Hosp, Dept Pediat, Bergen, Norway..
    Levy, Jonathan C.
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Mangino, Massimo
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Bonnycastle, Lori L.
    NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA..
    Schwarzmayr, Thomas
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Human Genet, Neuherberg, Germany..
    Fadista, Joao
    Lund Univ, Ctr Diabet, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden..
    Surdulescu, Gabriela L.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Herder, Christian
    Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Clin Diabetol, Dusseldorf, Germany.;German Ctr Diabet Res DZD, Neuherberg, Germany..
    Groves, Christopher J.
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Wieland, Thomas
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Human Genet, Neuherberg, Germany..
    Bork-Jensen, Jette
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Brandslund, Ivan
    Univ Southern Denmark, Inst Reg Hlth Res, Odense, Denmark.;Vejle Hosp, Dept Clin Biochem, Vejle, Denmark..
    Christensen, Cramer
    Vejle Hosp, Dept Internal Med & Endocrinol, Vejle, Denmark..
    Koistinen, Heikki A.
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.;Univ Helsinki, Abdominal Ctr Endocrinol, Helsinki, Finland.;Univ Helsinki, Cent Hosp, Helsinki, Finland.;Minerva Fdn, Helsinki, Finland.;Univ Helsinki, Dept Med, Helsinki, Finland..
    Doney, Alex S. F.
    Ninewells Hosp & Med Sch, Med Res Inst, Div Cardiovasc & Diabet Med, Dundee, Scotland..
    Kinnunen, Leena
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland..
    Esko, Tonu
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Harvard Med Sch, Dept Genet, Boston, MA USA.;Boston Childrens Hosp, Div Endocrinol, Boston, MA USA..
    Farmer, Andrew J.
    Univ Oxford, Nuffield Dept Primary Care Hlth Sci, Oxford, England..
    Hakaste, Liisa
    Univ Helsinki, Abdominal Ctr Endocrinol, Helsinki, Finland.;Univ Helsinki, Cent Hosp, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland.;Univ Helsinki, Res Programs Unit, Diabet & Obes, Helsinki, Finland..
    Hodgkiss, Dylan
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Kravic, Jasmina
    Lund Univ, Ctr Diabet, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden..
    Lyssenko, Valeriya
    Lund Univ, Ctr Diabet, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden..
    Hollensted, Mette
    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 Reg Denmark, Res Ctr Prevent & Hlth, Glostrup, Denmark.;Univ Copenhagen, Inst Hlth Sci, Dept Publ Hlth, Copenhagen, Denmark.;Aalborg Univ, Med, Aalborg, Denmark..
    Ladenvall, Claes
    Lund Univ, Ctr Diabet, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden..
    Justesen, Johanne Marie
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Karajamaki, Annemari
    Vaasa Cent Hosp, Dept Primary Hlth Care, Vaasa, Finland.;Vaasa Hlth Care Ctr, Ctr Diabet, Vaasa, Finland..
    Kriebel, Jennifer
    German Ctr Diabet Res DZD, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany..
    Rathmann, Wolfgang
    Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Biometr & Epidemiol, Dusseldorf, Germany..
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lauritzen, Torsten
    Aarhus Univ, Sect Gen Practice, Dept Publ Hlth, Aarhus, Denmark..
    Narisu, Narisu
    NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA..
    Linneberg, Allan
    Capital Reg Denmark, Res Ctr Prevent & Hlth, Glostrup, Denmark.;Rigshosp, Dept Clin Expt Res, Glostrup, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark..
    Melander, Olle
    Lund Univ, Dept Clin Sci Hypertens & Cardiovasc, Malmo, Sweden..
    Milani, Lili
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Neville, Matt
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    Orho-Melander, Marju
    Lund Univ, Dept Clin Sci Diabet & Cardiovasc Dis, Genet Epidemiol, Malmo, Sweden..
    Qi, Lu
    Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
    Qi, Qibin
    Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA..
    Roden, Michael
    Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Clin Diabetol, Dusseldorf, Germany.;German Ctr Diabet Res DZD, Neuherberg, Germany.;Univ Dusseldorf, Fac Med, Dept Endocrinol & Diabetol, Dusseldorf, Germany..
    Rolandsson, Olov
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Swift, Amy
    NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA..
    Rosengren, Anders H.
    Lund Univ, Ctr Diabet, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden..
    Stirrups, Kathleen
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambs, England..
    Wood, Andrew R.
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter, Devon, England..
    Mihailov, Evelin
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Blancher, Christine
    Univ Oxford, Nuffield Dept Med, Oxford Genom Ctr, High Throughput Genom,Wellcome Trust Ctr Human Ge, Oxford, England..
    Carneiro, Mauricio O.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Maguire, Jared
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Poplin, Ryan
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Shakir, Khalid
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Fennell, Timothy
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    DePristo, Mark
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    de Angelis, Martin Hrabe
    German Ctr Diabet Res DZD, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Expt Genet, Neuherberg, Germany.;Tech Univ Munich, Ctr Life & Food Sci Weihenstephan, Freising Weihenstephan, Germany..
    Deloukas, Panos
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England.;King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah, Saudi Arabia..
    Gjesing, Anette P.
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Jun, Goo
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX 77030 USA..
    Nilsson, Peter
    Lund Univ, Dept Clin Sci, Med, Malmo, Sweden..
    Murphy, Jacquelyn
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Onofrio, Robert
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Thorand, Barbara
    German Ctr Diabet Res DZD, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany..
    Hansen, Torben
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark.;Univ Southern Denmark, Fac Hlth Sci, Odense, Denmark..
    Meisinger, Christa
    German Ctr Diabet Res DZD, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany..
    Hu, Frank B.
    Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.;Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA..
    Isomaa, Bo
    Folkhalsan Res Ctr, Helsinki, Finland.;Dept Social Serv & Hlth Care, Pietarsaari, Finland..
    Karpe, Fredrik
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    Liang, Liming
    Harvard Sch Publ Hlth, Dept Biostat, Boston, MA USA.;Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA..
    Peters, Annette
    Munich Heart Alliance, DZHK German Ctr Cardiovasc Res, Munich, Germany.;German Ctr Diabet Res DZD, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany..
    Huth, Cornelia
    German Ctr Diabet Res DZD, Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany..
    O'Rahilly, Stephen P.
    Univ Cambridge, Inst Metab Sci, Metab Res Labs, Cambridge, England..
    Palmer, Colin N. A.
    Univ Dundee, Ninewells Hosp & Med Sch, Pat Macpherson Ctr Pharmacogenet & Pharmacogen, Dundee, Scotland..
    Pedersen, Oluf
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Rauramaa, Rainer
    Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio, Finland..
    Tuomilehto, Jaakko
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.;Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria.;King Abdulaziz Univ, Diabet Res Grp, Jeddah, Saudi Arabia.;Autonomous Univ Madrid, Univ Hosp LaPaz, Inst Invest Sanitaria Hosp Univ LaPaz IdiPAZ, Madrid, Spain.;Natl Inst Hlth & Welf, Helsinki, Finland..
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Helsinki, Finland..
    Watanabe, Richard M.
    Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA.;Univ Southern Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA USA.;Univ Southern Calif, Keck Sch Med, Dabet & Obes Res Inst, Los Angeles, CA USA..
    Syvanen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bergman, Richard N.
    Cedars Sinai Diabet & Obes Res Inst, Los Angeles, CA USA..
    Bharadwaj, Dwaipayan
    CSIR IGIB, Funct Genom Unit, New Delhi, India..
    Bottinger, Erwin P.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Cho, Yoon Shin
    Hallym Univ, Dept Biomed Sci, Chunchon, South Korea..
    Chandak, Giriraj R.
    CSIR Ctr Cellular & Mol Biol, Hyderabad, Telangana, India..
    Chan, Juliana C. N.
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Hong Kong, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Hong Kong Inst Diabet & Obes, Hong Kong, Hong Kong, Peoples R China..
    Chia, Kee Seng
    Natl Univ Hlth Syst, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Daly, Mark J.
    Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA..
    Ebrahim, Shah B.
    Ctr Chron Dis Control, New Delhi, India..
    Langenberg, Claudia
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Elliott, Paul
    Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England.;Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England..
    Jablonski, Kathleen A.
    George Washington Univ, Biostat Ctr, Rockville, MD USA..
    Lehman, Donna M.
    Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA..
    Jia, Weiping
    Shanghai Jiao Tong Univ, Peoples Hosp 6, Shanghai Diabet Inst, Dept Endocrinol & Metab, Shanghai, Peoples R China..
    Ma, Ronald C. W.
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Hong Kong, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Hong Kong Inst Diabet & Obes, Hong Kong, Hong Kong, Peoples R China..
    Pollin, Toni I.
    Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.;Univ Maryland, Sch Med, Program Personalized & Genom Med, Baltimore, MD 21201 USA..
    Sandhu, Manjinder
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambs, England.;Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England..
    Tandon, Nikhil
    All India Inst Med Sci, Dept Endocrinol & Metab, New Delhi, India..
    Froguel, Philippe
    Univ Lille, Lille Pasteur Inst, CNRS UMR8199, Lille, France.;Imperial Coll London, Sch Publ Hlth, Dept Genom Common Dis, London, England..
    Barroso, Ines
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambs, England.;Univ Cambridge, Inst Metab Sci, Metab Res Labs, Cambridge, England..
    Teo, Yik Ying
    Natl Univ Hlth Syst, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Natl Univ Singapore, Inst Life Sci, Singapore, Singapore.;Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore, Singapore..
    Zeggini, Eleftheria
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambs, England..
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Small, Kerrin S.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Ried, Janina S.
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany..
    DeFronzo, Ralph A.
    Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA..