Article

Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity

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Abstract

Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.

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References

  1. 1.

    Bray, G. A. & Ryan, D. H. Update on obesity pharmacotherapy. Ann. NY Acad. Sci. 1311, 1–13 (2014).

  2. 2.

    Bray, G. A., Frühbeck, G., Ryan, D. H. & Wilding, J. P. Management of obesity. Lancet 387, 1947–1956 (2016).

  3. 3.

    Monda, K. L. et al. A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry. Nat. Genet. 45, 690–696 (2013).

  4. 4.

    Wen, W. et al. Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index. Hum. Mol. Genet. 23, 5492–5504 (2014).

  5. 5.

    Locke, A. E. et al. Genetic studies of body mass index yield new insights for obesity biology. Nature 518, 197–206 (2015).

  6. 6.

    Winkler, T. W. et al. The influence of age and sex on genetic associations with adult body size and shape: a large-scale genome-wide interaction study. PLoS Genet. 11, e1005378 (2015).

  7. 7.

    Akiyama, M. et al. Genome-wide association study identifies 112 new loci for body mass index in the Japanese population. Nat. Genet. 49, 1458–1467 (2017).

  8. 8.

    van der Klaauw, A. A. & Farooqi, I. S. The hunger genes: pathways to obesity. Cell 161, 119–132 (2015).

  9. 9.

    Edwards, S. L., Beesley, J., French, J. D. & Dunning, A. M. Beyond GWASs: illuminating the dark road from association to function. Am. J. Hum. Genet. 93, 779–797 (2013).

  10. 10.

    Stratigopoulos, G. et al. Hypomorphism of Fto and Rpgrip1l causes obesity in mice. J. Clin. Invest. 126, 1897–1910 (2016).

  11. 11.

    Stratigopoulos, G., LeDuc, C. A., Cremona, M. L., Chung, W. K. & Leibel, R. L. Cut-like homeobox 1 (CUX1) regulates expression of the fat mass and obesity-associated and retinitis pigmentosa GTPase regulator–interacting protein-1-like (RPGRIP1L) genes and coordinates leptin receptor signaling. J. Biol. Chem. 286, 2155–2170 (2011).

  12. 12.

    Stratigopoulos, G. et al. Hypomorphism for RPGRIP1L, a ciliary gene vicinal to the FTO locus, causes increased adiposity in mice. Cell Metab. 19, 767–779 (2014).

  13. 13.

    Claussnitzer, M. et al. FTO obesity variant circuitry and adipocyte browning in humans. N. Engl. J. Med. 373, 895–907 (2015).

  14. 14.

    Smemo, S. et al. Obesity-associated variants within FTO form long-range functional connections with IRX3. Nature 507, 371–375 (2014).

  15. 15.

    Marouli, E. et al. Rare and low-frequency coding variants alter human adult height. Nature 542, 186–190 (2017).

  16. 16.

    Fuchsberger, C. et al. The genetic architecture of type 2 diabetes. Nature 536, 41–47 (2016).

  17. 17.

    Sina, M. et al. Phenotypes in three pedigrees with autosomal dominant obesity caused by haploinsufficiency mutations in the melanocortin-4 receptor gene. Am. J. Hum. Genet. 65, 1501–1507 (1999).

  18. 18.

    Pearce, L. R. et al. KSR2 mutations are associated with obesity, insulin resistance, and impaired cellular fuel oxidation. Cell 155, 765–777 (2013).

  19. 19.

    Hinney, A. et al. Several mutations in the melanocortin-4 receptor gene including a nonsense and a frameshift mutation associated with dominantly inherited obesity in humans. J. Clin. Endocrinol. Metab. 84, 1483–1486 (1999).

  20. 20.

    Purcell, S. M. et al. A polygenic burden of rare disruptive mutations in schizophrenia. Nature 506, 185–190 (2014).

  21. 21.

    van den Berg, L. et al. Melanocortin-4 receptor gene mutations in a Dutch cohort of obese children. Obesity 19, 604–611 (2011).

  22. 22.

    Surendran, P. et al. Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension. Nat. Genet. 48, 1151–1161 (2016).

  23. 23.

    Lunetta, K. L. et al. Rare coding variants and X-linked loci associated with age at menarche. Nat. Commun. 6, 7756 (2015).

  24. 24.

    Zhou, Z. et al. Cidea-deficient mice have lean phenotype and are resistant to obesity. Nat. Genet. 35, 49–56 (2003).

  25. 25.

    Tews, D. et al. Comparative gene array analysis of progenitor cells from human paired deep neck and subcutaneous adipose tissue. Mol. Cell. Endocrinol. 395, 41–50 (2014).

  26. 26.

    Stutzmann, F. et al. Non-synonymous polymorphisms in melanocortin-4 receptor protect against obesity: the two facets of a Janus obesity gene. Hum. Mol. Genet. 16, 1837–1844 (2007).

  27. 27.

    Lin, H. Q., Wang, Y., Chan, K. L., Ip, T. M. & Wan, C. C. Differential regulation of lipid metabolism genes in the brain of acetylcholinesterase knockout mice. J. Mol. Neurosci. 53, 397–408 (2014).

  28. 28.

    Vignaud, A. et al. Genetic ablation of acetylcholinesterase alters muscle function in mice. Chem. Biol. Interact. 175, 129–130 (2008).

  29. 29.

    Ji, Z., Mei, F. C. & Cheng, X. Epac, not PKA catalytic subunit, is required for 3T3-L1 preadipocyte differentiation. Front. Biosci. 2, 392–398 (2010).

  30. 30.

    Yan, J. et al. Enhanced leptin sensitivity, reduced adiposity, and improved glucose homeostasis in mice lacking exchange protein directly activated by cyclic AMP isoform 1. Mol. Cell. Biol. 33, 918–926 (2013).

  31. 31.

    Almahariq, M., Mei, F. C. & Cheng, X. Cyclic AMP sensor EPAC proteins and energy homeostasis. Trends Endocrinol. Metab. 25, 60–71 (2014).

  32. 32.

    Kai, A. K. et al. Exchange protein activated by cAMP 1 (Epac1)-deficient mice develop β-cell dysfunction and metabolic syndrome. FASEB J. 27, 4122–4135 (2013).

  33. 33.

    Hardie, D. G., Ross, F. A. & Hawley, S. A. AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat. Rev. Mol. Cell Biol. 13, 251–262 (2012).

  34. 34.

    Hardie, D. G. & Ashford, M. L. AMPK: regulating energy balance at the cellular and whole body levels. Physiology 29, 99–107 (2014).

  35. 35.

    López, M., Nogueiras, R., Tena-Sempere, M. & Diéguez, C. Hypothalamic AMPK: a canonical regulator of whole-body energy balance. Nat. Rev. Endocrinol. 12, 421–432 (2016).

  36. 36.

    Minokoshi, Y. et al. AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus. Nature 428, 569–574 (2004).

  37. 37.

    Viollet, B. et al. The AMP-activated protein kinase α2 catalytic subunit controls whole-body insulin sensitivity. J. Clin. Invest. 111, 91–98 (2003).

  38. 38.

    Xue, B. et al. Neuronal protein tyrosine phosphatase 1B deficiency results in inhibition of hypothalamic AMPK and isoform-specific activation of AMPK in peripheral tissues. Mol. Cell. Biol. 29, 4563–4573 (2009).

  39. 39.

    Warren, H. R. et al. Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk. Nat. Genet. 49, 403–415 (2017).

  40. 40.

    Chami, N. et al. Exome genotyping identifies pleiotropic variants associated with red blood cell traits. Am. J. Hum. Genet. 99, 8–21 (2016).

  41. 41.

    Li, M. et al. SOS2 and ACP1 loci identified through large-scale exome chip analysis regulate kidney development and function. J. Am. Soc. Nephrol. 28, 981–994 (2017).

  42. 42.

    Liu, C. et al. Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci. Nat. Genet. 48, 1162–1170 (2016).

  43. 43.

    Schwartz, M. W., Woods, S. C., Porte, D. Jr, Seeley, R. J. & Baskin, D. G. Central nervous system control of food intake. Nature 404, 661–671 (2000).

  44. 44.

    Garfield, A. S. et al. A neural basis for melanocortin-4 receptor–regulated appetite. Nat. Neurosci. 18, 863–871 (2015).

  45. 45.

    Huszar, D. et al. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 88, 131–141 (1997).

  46. 46.

    Fan, W., Boston, B. A., Kesterson, R. A., Hruby, V. J. & Cone, R. D. Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. Nature 385, 165–168 (1997).

  47. 47.

    Yeo, G. S. H. et al. A frameshift mutation in MC4R associated with dominantly inherited human obesity. Nat. Genet. 20, 111–112 (1998).

  48. 48.

    Vaisse, C., Clement, K., Guy-Grand, B. & Froguel, P. A frameshift mutation in human MC4R is associated with a dominant form of obesity. Nat. Genet. 20, 113–114 (1998).

  49. 49.

    Lubrano-Berthelier, C. et al. Melanocortin 4 receptor mutations in a large cohort of severely obese adults: prevalence, functional classification, genotype–phenotype relationship, and lack of association with binge eating. J. Clin. Endocrinol. Metab. 91, 1811–1818 (2006).

  50. 50.

    Farooqi, I. S. et al. Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N. Engl. J. Med. 348, 1085–1095 (2003).

  51. 51.

    Lek, M. et al. Analysis of protein-coding genetic variation in 60,706 humans. Nature 536, 285–291 (2016).

  52. 52.

    Hinney, A. et al. Melanocortin-4 receptor gene: case–control study and transmission disequilibrium test confirm that functionally relevant mutations are compatible with a major gene effect for extreme obesity. J. Clin. Endocrinol. Metab. 88, 4258–4267 (2003).

  53. 53.

    Speliotes, E. K. et al. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat. Genet. 42, 937–948 (2010).

  54. 54.

    Saxena, R. et al. Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. Nat. Genet. 42, 142–148 (2010).

  55. 55.

    Miyawaki, K. et al. Inhibition of gastric inhibitory polypeptide signaling prevents obesity. Nat. Med. 8, 738–742 (2002).

  56. 56.

    Hansotia, T. et al. Extrapancreatic incretin receptors modulate glucose homeostasis, body weight, and energy expenditure. J. Clin. Invest. 117, 143–152 (2007).

  57. 57.

    Fulurija, A. et al. Vaccination against GIP for the treatment of obesity. PLoS One 3, e3163 (2008).

  58. 58.

    Finan, B. et al. Reappraisal of GIP pharmacology for metabolic diseases. Trends Mol. Med. 22, 359–376 (2016).

  59. 59.

    Irwin, N. & Flatt, P. R. Evidence for beneficial effects of compromised gastric inhibitory polypeptide action in obesity-related diabetes and possible therapeutic implications. Diabetologia 52, 1724–1731 (2009).

  60. 60.

    Revelli, J. P. et al. Profound obesity secondary to hyperphagia in mice lacking kinase suppressor of ras 2. Obesity 19, 1010–1018 (2011).

  61. 61.

    Costanzo-Garvey, D. L. et al. KSR2 is an essential regulator of AMP kinase, energy expenditure, and insulin sensitivity. Cell Metab. 10, 366–378 (2009).

  62. 62.

    Brommage, R. et al. High-throughput screening of mouse knockout lines identifies true lean and obese phenotypes. Obesity 16, 2362–2367 (2008).

  63. 63.

    Liu, L. et al. Proteomic characterization of the dynamic KSR-2 interactome, a signaling scaffold complex in MAPK pathway. Biochim. Biophys. Acta 1794, 1485–1495 (2009).

  64. 64.

    Kühnen, P. et al. Proopiomelanocortin deficiency treated with a melanocortin-4 receptor agonist. N. Engl. J. Med. 375, 240–246 (2016).

  65. 65.

    Xiang, Y. Y., Dong, H., Yang, B. B., Macdonald, J. F. & Lu, W. Y. Interaction of acetylcholinesterase with neurexin-1β regulates glutamatergic synaptic stability in hippocampal neurons. Mol. Brain 7, 15 (2014).

  66. 66.

    Bartels, C. F., Zelinski, T. & Lockridge, O. Mutation at codon 322 in the human acetylcholinesterase (ACHE) gene accounts for YT blood group polymorphism. Am. J. Hum. Genet. 52, 928–936 (1993).

  67. 67.

    Farlow, M. R. et al. Effectiveness and tolerability of high-dose (23 mg/d) versus standard-dose (10 mg/d) donepezil in moderate to severe Alzheimer’s disease: a 24-week, randomized, double-blind study. Clin. Ther. 32, 1234–1251 (2010).

  68. 68.

    Farlow, M. et al. Safety and tolerability of donepezil 23 mg in moderate to severe Alzheimer’s disease. BMC Neurol. 11, 57 (2011).

  69. 69.

    Tariot, P., Salloway, S., Yardley, J., Mackell, J. & Moline, M. Long-term safety and tolerability of donepezil 23 mg in patients with moderate to severe Alzheimer’s disease. BMC Res. Notes 5, 283 (2012).

  70. 70.

    Hu, Y. et al. Role of exchange protein directly activated by cyclic AMP isoform 1 in energy homeostasis: regulation of leptin expression and secretion in white adipose tissue. Mol. Cell. Biol. 36, 2440–2450 (2016).

  71. 71.

    Altarejos, J. Y. et al. The Creb1 coactivator Crtc1 is required for energy balance and fertility. Nat. Med. 14, 1112–1117 (2008).

  72. 72.

    Winnier, D. A. et al. Transcriptomic identification of ADH1B as a novel candidate gene for obesity and insulin resistance in human adipose tissue in Mexican Americans from the Veterans Administration Genetic Epidemiology Study (VAGES). PLoS One 10, e0119941 (2015).

  73. 73.

    Molotkov, A., Deltour, L., Foglio, M. H., Cuenca, A. E. & Duester, G. Distinct retinoid metabolic functions for alcohol dehydrogenase genes Adh1 and Adh4 in protection against vitamin A toxicity or deficiency revealed in double null mutant mice. J. Biol. Chem. 277, 13804–13811 (2002).

  74. 74.

    GTEx Consortium. The Genotype-Tissue Expression (GTEx) pilot analysis: multitissue gene regulation in humans. Science 348, 648–660 (2015).

  75. 75.

    Volpicelli-Daley, L. A., Duysen, E. G., Lockridge, O. & Levey, A. I. Altered hippocampal muscarinic receptors in acetylcholinesterase-deficient mice. Ann. Neurol. 53, 788–796 (2003).

  76. 76.

    Ivanenkov, V. V., Murphy-Piedmonte, D. M. & Kirley, T. L. Bacterial expression, characterization, and disulfide bond determination of soluble human NTPDase6 (CD39L2) nucleotidase: implications for structure and function. Biochemistry 42, 11726–11735 (2003).

  77. 77.

    Jain, R. N. et al. Hip1r is expressed in gastric parietal cells and is required for tubulovesicle formation and cell survival in mice. J. Clin. Invest. 118, 2459–2470 (2008).

  78. 78.

    Engqvist-Goldstein, A. E. et al. RNAi-mediated Hip1R silencing results in stable association between the endocytic machinery and the actin assembly machinery. Mol. Biol. Cell 15, 1666–1679 (2004).

  79. 79.

    Tao, Y. X. The melanocortin-4 receptor: physiology, pharmacology, and pathophysiology. Endocr. Rev. 31, 506–543 (2010).

  80. 80.

    Stutzmann, F. et al. Prevalence of melanocortin-4 receptor deficiency in Europeans and their age-dependent penetrance in multigenerational pedigrees. Diabetes 57, 2511–2518 (2008).

  81. 81.

    Vaisse, C. et al. Melanocortin-4 receptor mutations are a frequent and heterogeneous cause of morbid obesity. J. Clin. Invest. 106, 253–262 (2000).

  82. 82.

    Schönke, M., Myers, M. G. Jr., Zierath, J. R. & Björnholm, M. Skeletal muscle AMP-activated protein kinase γ1H151R overexpression enhances whole body energy homeostasis and insulin sensitivity. Am. J. Physiol. Endocrinol. Metab. 309, E679–E690 (2015).

  83. 83.

    Pellinen, T. et al. Small GTPase Rab21 regulates cell adhesion and controls endosomal traffic of β1-integrins. J. Cell Biol. 173, 767–780 (2006).

  84. 84.

    Banerjee, U. & Cheng, X. Exchange protein directly activated by cAMP encoded by the mammalian rapgef3 gene: structure, function and therapeutics. Gene 570, 157–167 (2015).

  85. 85.

    Rippey, C. et al. Formation of chimeric genes by copy-number variation as a mutational mechanism in schizophrenia. Am. J. Hum. Genet. 93, 697–710 (2013).

  86. 86.

    Schmitz, C., Kinge, P. & Hutter, H. Axon guidance genes identified in a large-scale RNAi screen using the RNAi-hypersensitive Caenorhabditis elegans strain nre-1(hd20) lin-15b(hd126). Proc. Natl. Acad. Sci. USA 104, 834–839 (2007).

  87. 87.

    Setoguchi, R. et al. Repression of the transcription factor Th-POK by Runx complexes in cytotoxic T cell development. Science 319, 822–825 (2008).

  88. 88.

    Widom, R. L., Culic, I., Lee, J. Y. & Korn, J. H. Cloning and characterization of hcKrox, a transcriptional regulator of extracellular matrix gene expression. Gene 198, 407–420 (1997).

  89. 89.

    Sun, X. et al. Deletion of Atbf1/Zfhx3 in mouse prostate causes neoplastic lesions, likely by attenuation of membrane and secretory proteins and multiple signaling pathways. Neoplasia 16, 377–389 (2014).

  90. 90.

    Parsons, M. J. et al. The regulatory factor ZFHX3 modifies circadian function in SCN via an AT motif–driven axis. Cell 162, 607–621 (2015).

  91. 91.

    Balzani, E. et al. The Zfhx3-mediated axis regulates sleep and interval timing in mice. Cell Rep. 16, 615–621 (2016).

  92. 92.

    Kao, Y. H. et al. ZFHX3 knockdown increases arrhythmogenesis and dysregulates calcium homeostasis in HL-1 atrial myocytes. Int. J. Cardiol. 210, 85–92 (2016).

  93. 93.

    Auer, P. L., Reiner, A. P. & Leal, S. M. The effect of phenotypic outliers and non-normality on rare-variant association testing. Eur. J. Hum. Genet. 24, 1188–1194 (2016).

  94. 94.

    Goldstein, J. I. et al. zCall: a rare variant caller for array-based genotyping: genetics and population analysis. Bioinformatics 28, 2543–2545 (2012).

  95. 95.

    Grove, M. L. et al. Best practices and joint calling of the HumanExome BeadChip: the CHARGE Consortium. PLoS One 8, e68095 (2013).

  96. 96.

    Zhan, X., Hu, Y., Li, B., Abecasis, G. R. & Liu, D. J. RVTESTS: an efficient and comprehensive tool for rare variant association analysis using sequence data. Bioinformatics 32, 1423–1426 (2016).

  97. 97.

    Liu, D. J. et al. Meta-analysis of gene-level tests for rare variant association. Nat. Genet. 46, 200–204 (2014).

  98. 98.

    Winkler, T. W. et al. Quality control and conduct of genome-wide association meta-analyses. Nat. Protoc. 9, 1192–1212 (2014).

  99. 99.

    Winkler, T. W. et al. EasyStrata: evaluation and visualization of stratified genome-wide association meta-analysis data. Bioinformatics 31, 259–261 (2015).

  100. 100.

    Wu, M. C. et al. Rare-variant association testing for sequencing data with the sequence kernel association test. Am. J. Hum. Genet. 89, 82–93 (2011).

  101. 101.

    Price, A. L. et al. Pooled association tests for rare variants in exon-resequencing studies. Am. J. Hum. Genet. 86, 832–838 (2010).

  102. 102.

    Kiezun, A. et al. Exome sequencing and the genetic basis of complex traits. Nat. Genet. 44, 623–630 (2012).

  103. 103.

    Feng, S., Liu, D., Zhan, X., Wing, M. K. & Abecasis, G. R. RAREMETAL: fast and powerful meta-analysis for rare variants. Bioinformatics 30, 2828–2829 (2014).

  104. 104.

    Yang, J. et al. Genomic inflation factors under polygenic inheritance. Eur. J. Hum. Genet. 19, 807–812 (2011).

  105. 105.

    Willer, C. J., Li, Y. & Abecasis, G. R. METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics 26, 2190–2191 (2010).

  106. 106.

    Thorleifsson, G. et al. Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat. Genet. 41, 18–24 (2009).

  107. 107.

    Denny, J. C. et al. PheWAS: demonstrating the feasibility of a phenome-wide scan to discover gene–disease associations. Bioinformatics 26, 1205–1210 (2010).

  108. 108.

    Pers, T. H. et al. Biological interpretation of genome-wide association studies using predicted gene functions. Nat. Commun. 6, 5890 (2015).

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Acknowledgements

A.P.R. was supported by R01DK089256. A.W.H. is supported by an NHMRC Practitioner Fellowship (APP1103329). A.K.M. received funding from NIH/NIDDK K01DK107836. A.T.H. is a Wellcome Trust Senior Investigator (WT098395) and an NIH Research Senior Investigator. A.P.M. is a Wellcome Trust Senior Fellow in Basic Biomedical Science (WT098017). A.R.W. is supported by the European Research Council (SZ-245 50371-GLUCOSEGENES-FP7-IDEAS-ERC). A.U.J. is supported by the American Heart Association (13POST16500011) and the NIH (R01DK089256, R01DK101855, K99HL130580). B.K. and E.K.S. were supported by the Doris Duke Medical Foundation, the NIH (R01DK106621), the University of Michigan Internal Medicine Department, Division of Gastroenterology, the University of Michigan Biological Sciences Scholars Program and the Central Society for Clinical Research. C.J.W. is supported by the NIH (HL094535, HL109946). D.J.L. is supported by R01HG008983 and R21DA040177. D.R.W. is supported by the Danish Diabetes Academy, which is funded by the Novo Nordisk Foundation. V. Salomaa has been supported by the Finnish Foundation for Cardiovascular Research. F.W.A. is supported by Dekker scholarship–Junior Staff Member 2014T001 Netherlands Heart Foundation and the UCL Hospitals NIHR Biomedical Research Centre. F.D. is supported by the UK MRC (MC_UU_12013/1-9). G.C.-P. received scholarship support from the University of Queensland and QIMR Berghofer. G.L. is funded by the Montreal Heart Institute Foundation and the Canada Research Chair program. H.Y. and T.M.F. are supported by the European Research Council (323195; SZ-245 50371-GLUCOSEGENES-FP7-IDEAS-ERC). I.M.H. is supported by BMBF (01ER1206) and BMBF (01ER1507m), the NIH and the Max Planck Society. J. Haessler was supported by NHLBI R21HL121422. J.N.H. is supported by NIH R01DK075787. K.E.N. was supported by the NIH (R01DK089256, R01HD057194, U01HG007416, R01DK101855) and the American Heart Association (13GRNT16490017). M.A.R. is supported by the Nuffield Department of Clinical Medicine Award, Clarendon Scholarship. M.I.M. is a Wellcome Trust Senior Investigator (WT098381) and an NIH Research Senior Investigator. M.D. is supported by the NCI (R25CA94880, P30CA008748). P.R.N. is supported by the European Research Council (AdG; 293574), the Research Council of Norway, the University of Bergen, the KG Jebsen Foundation and the Helse Vest, Norwegian Diabetes Association. P.T.E. is supported by the NIH (1R01HL092577, R01HL128914, K24HL105780), by an Established Investigator Award from the American Heart Association (13EIA14220013) and by the Foundation Leducq (14CVD01). P.L.A. was supported by NHLBI R21HL121422 and R01DK089256. P.L.H. is supported by the NIH (NS33335, HL57818). R.S.F. is supported by the NIH (T32GM096911). R.J.F.L. is supported by the NIH (R01DK110113, U01HG007417, R01DK101855, R01DK107786). S.A.L. is supported by the NIH (K23HL114724) and a Doris Duke Charitable Foundation Clinical Scientist Development Award. T.D.S. holds an ERC Advanced Principal Investigator award. T.A.M. is supported by an NHMRC Fellowship (APP1042255). T.H.P. received Lundbeck Foundation and Benzon Foundation support. V.T. is supported by a postdoctoral fellowship from the Canadian Institutes of Health Research (CIHR). Z.K. is supported by the Leenaards Foundation, the Swiss National Science Foundation (31003A-143914) and SystemsX.ch (51RTP0_151019). Part of this work was conducted using the UK Biobank resource (project numbers 1251 and 9072). A full list of acknowledgments appears in the Supplementary Note.

Author information

Author notes

  1. A list of members and affiliations appears in the Supplementary Note.

  2. Valérie Turcot, Yingchang Lu, Heather M. Highland, Claudia Schurmann, Anne E. Justice and Rebecca S. Fine contributed equally to this work.

  3. Guillaume Lettre, Kari E. North, Cecilia M. Lindgren, Joel N. Hirschhorn and Ruth J. F. Loos jointly directed this work.

Affiliations

  1. Montreal Heart Institute, Université de Montréal, Montreal, Quebec, Canada

    • Valérie Turcot
    • , Marie-Pierre Dubé
    • , Ken S. Lo
    • , John D. Rioux
    • , Jean-Claude Tardif
    •  & Guillaume Lettre
  2. Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN, USA

    • Yingchang Lu
  3. Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    • Yingchang Lu
    • , Claudia Schurmann
    • , Tamuno Alfred
    • , Erwin P. Bottinger
    •  & Ruth J. F. Loos
  4. Genetics of Obesity and Related Metabolic Traits Program, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    • Yingchang Lu
    • , Claudia Schurmann
    •  & Ruth J. F. Loos
  5. Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA

    • Heather M. Highland
    • , Anne E. Justice
    • , Mariaelisa Graff
    • , Kristin L. Young
    •  & Angela L. Mazul
  6. Human Genetics Center, University of Texas School of Public Health, University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, Houston, TX, USA

    • Heather M. Highland
  7. Broad Institute of MIT and Harvard, Cambridge, MA, USA

    • Rebecca S. Fine
    • , Tõnu Esko
    • , Alisa K. Manning
    • , Sailaja Vedantam
    • , Daniel I. Chasman
    • , Patrick T. Ellinor
    • , Jose C. Florez
    • , Sekar Kathiresan
    • , Steven A. Lubitz
    • , Aniruddh P. Patel
    • , Manuel A. Rivas
    •  & Joel N. Hirschhorn
  8. Department of Genetics, Harvard Medical School, Boston, MA, USA

    • Rebecca S. Fine
    • , Sailaja Vedantam
    •  & Joel N. Hirschhorn
  9. Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children’s Hospital, Boston, MA, USA

    • Rebecca S. Fine
    • , Tõnu Esko
    • , Sailaja Vedantam
    •  & Joel N. Hirschhorn
  10. Center for Applied Genomics, Division of Human Genetics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    • Jonathan P. Bradfield
    • , Struan F. A. Grant
    •  & Hakon Hakonarson
  11. Quantinuum Research, LLC, San Diego, CA, USA

    • Jonathan P. Bradfield
  12. Estonian Genome Center, University of Tartu, Tartu, Estonia

    • Tõnu Esko
    • , Lili Milani
    •  & Markus Perola
  13. Division of Epidemiology, Department of Medicine, Institute for Medicine and Public Health, Vanderbilt Genetics Institute, Vanderbilt University, Nashville, TN, USA

    • Ayush Giri
    •  & Todd L. Edwards
  14. Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical Center, Torrance, CA, USA

    • Xiuqing Guo
    • , Yii-Der I. Chen
    • , Yucheng Jia
    • , Eric Kim
    • , Kent D. Taylor
    • , Jie Yao
    •  & Jerome I. Rotter
  15. Wellcome Trust Sanger Institute, Hinxton, UK

    • Audrey E. Hendricks
    • , Inês Barroso
    • , John Danesh
    • , Gaëlle Marenne
    • , Lorraine Southam
    •  & Eleftheria Zeggini
  16. Department of Mathematical and Statistical Sciences, University of Colorado, Denver, CO, USA

    • Audrey E. Hendricks
  17. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK

    • Tugce Karaderi
    • , Anubha Mahajan
    • , Wei Gan
    • , Hidetoshi Kitajima
    • , Mark I. McCarthy
    • , Andrew P. Morris
    • , Neil R. Robertson
    • , Lorraine Southam
    • , Krina T Zondervan
    •  & Cecilia M. Lindgren
  18. Department of Biological Sciences, Faculty of Arts and Sciences, Eastern Mediterranean University, Famagusta, Cyprus

    • Tugce Karaderi
  19. Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany

    • Adelheid Lempradl
    •  & John A. Pospisilik
  20. Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA

    • Adam E. Locke
    • , Gonçalo Abecasis
    • , Michael Boehnke
    • , Shuang Feng
    • , Anne U. Jackson
    • , Xueling Sim
    •  & Heather M. Stringham
  21. McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA

    • Adam E. Locke
  22. William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK

    • Eirini Marouli
    • , Sameer E. Alharthi
    • , Mark J. Caulfield
    • , Stavroula Kanoni
    • , Patricia B. Munroe
    • , Kathleen E. Stirrups
    • , Helen R. Warren
    •  & Panos Deloukas
  23. Department of Vascular Medicine, AMC, Amsterdam, The Netherlands

    • Suthesh Sivapalaratnam
    •  & G. Kees Hovingh
  24. Massachusetts General Hospital, Boston, MA, USA

    • Suthesh Sivapalaratnam
    • , Alisa K. Manning
    • , Patrick T. Ellinor
    • , Jose C. Florez
    • , Paul L. Huang
    • , Sekar Kathiresan
    • , Steven A. Lubitz
    •  & Aniruddh P. Patel
  25. Department of Haematology, University of Cambridge, Cambridge, UK

    • Suthesh Sivapalaratnam
    •  & Kathleen E. Stirrups
  26. Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA

    • Mary F. Feitosa
    •  & Ingrid B. Borecki
  27. Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, UK

    • Nicholas G. D. Masca
    • , Christopher P. Nelson
    •  & Nilesh J. Samani
  28. NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK

    • Nicholas G. D. Masca
    • , Christopher P. Nelson
    •  & Nilesh J. Samani
  29. Department of Medicine, Harvard Medical School, Boston, MA, USA

    • Alisa K. Manning
    •  & Jose C. Florez
  30. Medical and Population Genetics Program, Broad Institute, Cambridge, MA, USA

    • Alisa K. Manning
    • , Patrick T. Ellinor
    • , Jose C. Florez
    •  & Steven A. Lubitz
  31. Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands

    • Carolina Medina-Gomez
    • , Oscar H. Franco
    • , M. Arfan Ikram
    • , André G. Uitterlinden
    • , Cornelia M. Duijn
    •  & Fernando Rivadeneira
  32. Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands

    • Carolina Medina-Gomez
    • , Linda Broer
    • , André G. Uitterlinden
    •  & Fernando Rivadeneira
  33. Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, USA

    • Poorva Mudgal
    • , Maggie C. Y. Ng
    • , Donald W. Bowden
    •  & Amanda J. Cox
  34. Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, USA

    • Maggie C. Y. Ng
    • , Donald W. Bowden
    •  & Amanda J. Cox
  35. Department of Epidemiology, University of Washington, Seattle, WA, USA

    • Alex P. Reiner
  36. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    • Alex P. Reiner
    • , Mengmeng Du
    • , Jeff Haessler
    •  & Charles Kooperberg
  37. MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge, UK

    • Sara M. Willems
    • , Claudia Langenberg
    • , Jian’an Luan
    • , John R. B. Perry
    • , Robert A. Scott
    • , Nicholas J. Wareham
    •  & Jing Hua Zhao
  38. Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany

    • Thomas W. Winkler
    • , Mathias Gorski
    •  & Iris M. Heid
  39. Netherlands Comprehensive Cancer Organisation, Utrecht, The Netherlands

    • Katja K. Aben
  40. Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands

    • Katja K. Aben
    • , Tessel E. Galesloot
    • , Lambertus A. Kiemeney
    •  & Sita H. Vermeulen
  41. School of Kinesiology and Health Science, Faculty of Health, York University, Toronto, Ontario, Canada

    • Dewan S. Alam
  42. Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia

    • Sameer E. Alharthi
    •  & Panos Deloukas
  43. Department of Family Medicine and Public Health, University of California, San Diego, La Jolla, CA, USA

    • Matthew Allison
  44. INSERM U1167, Lille, France

    • Philippe Amouyel
  45. Institut Pasteur de Lille, U1167, Lille, France

    • Philippe Amouyel
  46. Université de Lille, U1167, RID-AGE, Risk Factors and Molecular Determinants of Aging-Related Diseases, Lille, France

    • Philippe Amouyel
  47. Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands

    • Folkert W. Asselbergs
    •  & Jessica van Setten
  48. Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands

    • Folkert W. Asselbergs
  49. Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, UK

    • Folkert W. Asselbergs
  50. Zilber School of Public Health, University of Wisconsin–Milwaukee, Milwaukee, WI, USA

    • Paul L. Auer
  51. INSERM U1018, Centre de Recherche en Épidémiologie et Santé des Populations (CESP), Villejuif, France

    • Beverley Balkau
  52. Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark

    • Lia E. Bang
  53. Metabolic Research Laboratories, University of Cambridge, Cambridge, UK

    • Inês Barroso
    • , I. Sadaf Farooqi
    •  & Vanisha Mistry
  54. NIHR Cambridge Biomedical Research Centre, Wellcome Trust–MRC Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, UK

    • Inês Barroso
    • , I. Sadaf Farooqi
    •  & Vanisha Mistry
  55. Department of Biomedical Informatics, Vanderbilt University, Nashville, TN, USA

    • Lisa Bastarache
    •  & Josh C. Denny
  56. Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark

    • Marianne Benn
    • , Pia R. Kamstrup
    • , Sune F. Nielsen
    • , Børge G. Nordestgaard
    •  & Anette Varbo
  57. Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    • Marianne Benn
    • , Ruth Frikke-Schmidt
    • , Torben Jørgensen
    • , Sune F. Nielsen
    • , Børge G. Nordestgaard
    • , Anne Tybjaerg-Hansen
    •  & Anette Varbo
  58. Department of Computational Biology, University of Lausanne, Lausanne, Switzerland

    • Sven Bergmann
    •  & David Lamparter
  59. Swiss Institute of Bioinformatics, Lausanne, Switzerland

    • Sven Bergmann
    • , Zoltán Kutalik
    •  & David Lamparter
  60. Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA

    • Lawrence F. Bielak
    • , Sharon L. R. Kardia
    • , Patricia A. Peyser
    • , Erin B. Ware
    •  & Wei Zhao
  61. IFB Adiposity Diseases, University of Leipzig, Leipzig, Germany

    • Matthias Blüher
    • , Peter Kovacs
    •  & Michael Stumvoll
  62. Department of Medicine, University of Leipzig, Leipzig, Germany

    • Matthias Blüher
    •  & Michael Stumvoll
  63. Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Nuthetal, Germany

    • Heiner Boeing
  64. School of Public Health, Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX, USA

    • Eric Boerwinkle
    •  & Megan L. Grove
  65. Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA

    • Eric Boerwinkle
  66. Department of Nephrology, University Hospital Regensburg, Regensburg, Germany

    • Carsten A. Böger
    • , Mathias Gorski
    •  & Myriam Rheinberger
  67. Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    • Jette Bork-Jensen
    • , Anette P. Gjesing
    • , Niels Grarup
    • , Torben Hansen
    • , Christian T. Have
    • , Oluf Pedersen
    • , Tune H. Pers
    •  & Henrik Vestergaard
  68. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands

    • Michiel L. Bots
    •  & Paul I. W. Bakker
  69. Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA

    • Donald W. Bowden
    •  & Nicholette D. Palmer
  70. Department of Clinical Biochemistry, Lillebaelt Hospital, Vejle, Denmark

    • Ivan Brandslund
  71. Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark

    • Ivan Brandslund
  72. MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK

    • Gerome Breen
  73. NIHR Biomedical Research Centre for Mental Health, South London and Maudsley Hospital, London, UK

    • Gerome Breen
  74. Marshfield Clinic Research Institute, Marshfield, WI, USA

    • Murray H. Brilliant
    • , Peggy L. Peissig
    •  & Thomas N. Person
  75. Department of Medical Sciences, University of Trieste, Trieste, Italy

    • Marco Brumat
    • , Paolo Gasparini
    •  & Dragana Vuckovic
  76. Department of Medicine, University of Washington, Seattle, WA, USA

    • Amber A. Burt
    • , Gail P. Jarvik
    •  & Eric B. Larson
  77. MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK

    • Adam S. Butterworth
    • , Rajiv Chowdhury
    • , John Danesh
    • , Emanuele Angelantonio
    • , Joanna M. M. Howson
    • , Praveen Surendran
    •  & Robin Young
  78. NIHR Blood and Transplant Research Unit in Donor Health and Genomics, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK

    • Adam S. Butterworth
    • , John Danesh
    • , Emanuele Angelantonio
    • , Carmel Moore
    •  & David J. Roberts
  79. Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA

    • Peter T. Campbell
  80. Institute for Maternal and Child Health, IRCCS ‘Burlo Garofolo’, Trieste, Italy

    • Stefania Cappellani
    • , Eulalia Catamo
    • , Angela D’Eustacchio
    • , Paolo Gasparini
    • , Antonietta Robino
    •  & Dragana Vuckovic
  81. Weis Center for Research, Geisinger Health System, Danville, PA, USA

    • David J. Carey
    • , Helena Kuivaniemi
    •  & Gerard Tromp
  82. NIHR Barts Cardiovascular Research Unit, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK

    • Mark J. Caulfield
    • , Patricia B. Munroe
    •  & Helen R. Warren
  83. Department of Cardiology, London North West Healthcare NHS Trust, Ealing Hospital, Middlesex, UK

    • John C. Chambers
    • , Jaspal S. Kooner
    •  & Weihua Zhang
  84. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK

    • John C. Chambers
    • , Evangelos Evangelou
    • , Marcelo P. Segura-Lepe
    •  & Weihua Zhang
  85. Imperial College Healthcare NHS Trust, London, UK

    • John C. Chambers
    •  & Jaspal S. Kooner
  86. Division of Genetics, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    • Daniel I. Chasman
  87. Division of Preventive Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    • Daniel I. Chasman
    •  & Paul M. Ridker
  88. Harvard Medical School, Boston, MA, USA

    • Daniel I. Chasman
    • , Sekar Kathiresan
    • , Aniruddh P. Patel
    •  & Paul M. Ridker
  89. Medical Department, Lillebaelt Hospital, Vejle, Denmark

    • Cramer Christensen
  90. NHLBI Framingham Heart Study, Framingham, MA, USA

    • Audrey Y. Chu
    •  & Nancy L. Heard-Costa
  91. Genetics and Pharmacogenomics, Merck, Sharp & Dohme, Boston, MA, USA

    • Audrey Y. Chu
    •  & Dermot F. Reilly
  92. Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy

    • Massimiliano Cocca
  93. Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, US National Institutes of Health, Bethesda, MD, USA

    • Francis S. Collins
    • , Narisu Narisu
    •  & Amy J. Swift
  94. Department of Biostatistics, University of Liverpool, Liverpool, UK

    • James P. Cook
    • , Gail Davies
    • , Ian J. Deary
    •  & Andrew P. Morris
  95. Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK

    • Janie Corley
    • , Gail Davies
    • , Ian J. Deary
    •  & John M. Starr
  96. Department of Psychology, University of Edinburgh, Edinburgh, UK

    • Janie Corley
    •  & Alison Pattie
  97. Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands

    • Jordi Corominas Galbany
  98. Department of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands

    • Jordi Corominas Galbany
    •  & Anneke I. Hollander
  99. Menzies Health Institute Queensland, Griffith University, Southport, Queensland, Australia

    • Amanda J. Cox
  100. Department of Biomedical Informatics and Medical Education, University of Washington, Seattle, WA, USA

    • David S. Crosslin
  101. Diamantina Institute, University of Queensland, Brisbane, Queensland, Australia

    • Gabriel Cuellar-Partida
  102. QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia

    • Gabriel Cuellar-Partida
    • , Sarah E. Medland
    • , Grant W. Montgomery
    • , Dale R. Nyholt
    •  & Yadav Sapkota
  103. British Heart Foundation Cambridge Centre of Excellence, Department of Medicine, University of Cambridge, Cambridge, UK

    • John Danesh
  104. Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands

    • Paul I. W. Bakker
  105. Department of Clinical Chemistry and Haematology, Division of Laboratory and Pharmacy, University Medical Center Utrecht, Utrecht, The Netherlands

    • Mark C. H. Groot
  106. Utrecht Institute for Pharmaceutical Sciences, Division Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht, The Netherlands

    • Mark C. H. Groot
  107. Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands

    • Renée Mutsert
    • , Ruifang Li-Gao
    •  & Dennis O. Mook-Kanamori
  108. Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece

    • George Dedoussis
    •  & Aliki-Eleni Farmaki
  109. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA

    • Ellen W. Demerath
    •  & Pamela J. Schreiner
  110. Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands

    • Martin Heijer
  111. Laboratory of Experimental Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands

    • Hester M. Ruijter
    • , Gerard Pasterkamp
    •  & Sander W. Laan
  112. Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK

    • Joe G. Dennis
    • , Douglas F. Easton
    •  & Deborah J. Thompson
  113. Institute of Cardiovascular Science, University College London, London, UK

    • Fotios Drenos
  114. MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK

    • Fotios Drenos
    •  & Katherine E. Tansey
  115. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    • Mengmeng Du
  116. Department of Medicine, Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada

    • Marie-Pierre Dubé
    • , John D. Rioux
    •  & Guillaume Lettre
  117. Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK

    • Alison M. Dunning
    • , Douglas F. Easton
    • , Ailith Pirie
    •  & Jonathan P. Tyrer
  118. Institute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany

    • David Ellinghaus
    •  & Andre Franke
  119. Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK

    • Paul Elliott
  120. Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece

    • Evangelos Evangelou
  121. Department of Health Sciences, University of Leicester, Leicester, UK

    • Aliki-Eleni Farmaki
  122. Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA

    • Jessica D. Faul
    •  & Erin B. Ware
  123. Department of Ophthalmology, University of Cologne, Cologne, Germany

    • Sascha Fauser
  124. CNR Institute of Clinical Physiology, Pisa, Italy

    • Ele Ferrannini
  125. Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

    • Ele Ferrannini
  126. Toulouse University School of Medicine, Toulouse, France

    • Jean Ferrieres
  127. University of Glasgow, Glasgow, UK

    • Ian Ford
    • , Chris J. Packard
    • , Sandosh Padmanabhan
    • , Naveed Sattar
    •  & Robin Young
  128. Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA

    • Myriam Fornage
    •  & Li-An Lin
  129. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmo, Sweden

    • Paul W. Franks
    • , Frida Renström
    •  & Tibor V. Varga
  130. Department of Nutrition, Harvard School of Public Health, Boston, MA, USA

    • Paul W. Franks
  131. Department of Public Health and Clinical Medicine, Unit of Medicine, Umeå University, Umeå, Sweden

    • Paul W. Franks
  132. Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany

    • Nele Friedrich
  133. Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark

    • Ruth Frikke-Schmidt
    •  & Anne Tybjaerg-Hansen
  134. Research Unit, AREA Science Park, Trieste, Italy

    • Ilaria Gandin
  135. Centre for Biological Sciences, Faculty of Natural and Environmental Sciences, University of Southampton, Southampton, UK

    • Jane Gibson
  136. Geriatrics, Department of Public Health, Uppsala University, Uppsala, Sweden

    • Vilmantas Giedraitis
  137. Carolina Population Center, University of North Carolina, Chapel Hill, NC, USA

    • Penny Gordon-Larsen
    •  & Kathleen Mullan Harris
  138. Department of Nutrition, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA

    • Penny Gordon-Larsen
  139. Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany

    • Hans-Jörgen Grabe
  140. German Center for Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Greifswald, Germany

    • Hans-Jörgen Grabe
  141. Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    • Struan F. A. Grant
    •  & Hakon Hakonarson
  142. Division of Endocrinology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    • Struan F. A. Grant
  143. Vision Sciences, Clinical Neurosciences Research Group, Faculty of Medicine, University of Southampton, Southampton, UK

    • Helen L. Griffiths
    •  & Andrew J. Lotery
  144. Faculty of Medicine, University of Iceland, Reykjavik, Iceland

    • Vilmundur Gudnason
    • , Albert V. Smith
    • , Kari Stefansson
    •  & Unnur Thorsteinsdottir
  145. Icelandic Heart Association, Kopavogur, Iceland

    • Vilmundur Gudnason
    •  & Albert V. Smith
  146. Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden

    • Stefan Gustafsson
    •  & Erik Ingelsson
  147. Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, Amsterdam, The Netherlands

    • Anke R. Hammerschlag
    •  & Tinca J. Polderman
  148. Department of Sociology, University of North Carolina, Chapel Hill, NC, USA

    • Kathleen Mullan Harris
  149. Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Intramural Research Program, US National Institutes of Health, Bethesda, MD, USA

    • Tamara B. Harris
  150. University of Exeter Medical School, University of Exeter, Exeter, UK

    • Andrew T. Hattersley
  151. MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK

    • Caroline Hayward
    • , Jennifer E. Huffman
    •  & Veronique Vitart
  152. Biodemography of Aging Research Unit, Social Science Research Institute, Duke University, Durham, NC, USA

    • Liang He
    •  & Liang Sun
  153. Department of Public Health, University of Helsinki, Helsinki, Finland

    • Liang He
    • , Jaakko Kaprio
    • , Tellervo Korhonen
    • , Anu Loukola
    •  & Liang Sun
  154. Department of Neurology, Boston University School of Medicine, Boston, MA, USA

    • Nancy L. Heard-Costa
  155. Department of Psychiatry, Washington University, St. Louis, MO, USA

    • Andrew C. Heath
  156. Institute of Genetic Epidemiology, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany

    • Iris M. Heid
    • , Martina Müller-Nurasyid
    •  & Konstantin Strauch
  157. Department of Pediatrics, Haukeland University Hospital, Bergen, Norway

    • Øyvind Helgeland
    •  & Pål R. Njølstad
  158. KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway

    • Øyvind Helgeland
    • , Stefan Johansson
    •  & Pål R. Njølstad
  159. Department of Cardiology, Heart Center, Tampere University Hospital and Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland

    • Jussi Hernesniemi
    •  & Kjell Nikus
  160. Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland

    • Jussi Hernesniemi
    • , Terho Lehtimäki
    •  & Leo-Pekka Lyytikäinen
  161. Department of Clinical Chemistry, Finnish Cardiovascular Research Center–Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland

    • Jussi Hernesniemi
    • , Terho Lehtimäki
    •  & Leo-Pekka Lyytikäinen
  162. Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, Victoria, Australia

    • Alex W. Hewitt
  163. Centre for Ophthalmology and Vision Science, Lions Eye Institute, University of Western Australia, Perth, Western Australia, Australia

    • Alex W. Hewitt
  164. Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia

    • Alex W. Hewitt
  165. KG Jebsen Center for Genetic Epidemiology, Department of Public Health, NTNU, Norwegian University of Science and Technology, Trondheim, Norway

    • Oddgeir L. Holmen
  166. Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, China

    • Yao Hu
    • , Huaixing Li
    • , Xu Lin
    • , Feijie Wang
    • , Yiqin Wang
    •  & Pang Yao
  167. Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands

    • M. Arfan Ikram
  168. Department of Radiology, Erasmus Medical Center, Rotterdam, The Netherlands

    • M. Arfan Ikram
  169. Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA

    • Erik Ingelsson
    •  & Jin Li
  170. Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

    • Jan-Håkan Jansson
    •  & Olov Rolandsson
  171. Research Unit Skellefteå, Skellefteå, Sweden

    • Jan-Håkan Jansson
  172. Department of Genome Sciences, University of Washington, Seattle, WA, USA

    • Gail P. Jarvik
  173. Copenhagen City Heart Study, Frederiksberg Hospital, Frederiksberg, Denmark

    • Gorm B. Jensen
  174. Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway

    • Stefan Johansson
  175. National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark

    • Marit E. Jørgensen
  176. Steno Diabetes Center Copenhagen, Gentofte, Denmark

    • Marit E. Jørgensen
    •  & Henrik Vestergaard
  177. Faculty of Medicine, Aalborg University, Aalborg, Denmark

    • Torben Jørgensen
  178. Research Center for Prevention and Health, Capital Region of Denmark, Glostrup, Denmark

    • Torben Jørgensen
    • , Allan Linneberg
    •  & Betina H. Thuesen
  179. Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands

    • J. Wouter Jukema
    •  & Stella Trompet
  180. Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands

    • J. Wouter Jukema
  181. Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA

    • Bratati Kahali
    • , Elizabeth K. Speliotes
    • , Cristen J. Willer
    •  & Wei Zhou
  182. Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA

    • Bratati Kahali
    • , Elizabeth K. Speliotes
    • , Cristen J. Willer
    •  & Wei Zhou
  183. Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA

    • Bratati Kahali
    •  & Elizabeth K. Speliotes
  184. Centre for Brain Research, Indian Institute of Science, Bangalore, India

    • Bratati Kahali
  185. Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands

    • René S. Kahn
    •  & Roel A. Ophoff
  186. Department of Clinical Physiology, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland

    • Mika Kähönen
  187. Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland

    • Mika Kähönen
  188. Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland

    • Jaakko Kaprio
    • , Anu Loukola
    •  & Markus Perola
  189. National Institute for Health and Welfare, Helsinki, Finland

    • Jaakko Kaprio
    • , Tellervo Korhonen
    • , Kari Kuulasmaa
    • , Jaana Lindström
    • , Satu Männistö
    • , Markus Perola
    • , Veikko Salomaa
    •  & Jaakko Tuomilehto
  190. Echinos Medical Centre, Echinos, Greece

    • Maria Karaleftheri
  191. Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK

    • Fredrik Karpe
    • , Mark I. McCarthy
    • , Matt Neville
    • , Katharine R. Owen
    •  & Neil R. Robertson
  192. Oxford NIHR Biomedical Research Centre, Oxford University Hospitals Trust, Oxford, UK

    • Fredrik Karpe
    • , Mark I. McCarthy
    • , Matt Neville
    •  & Katharine R. Owen
  193. UKCRC Centre of Excellence for Public Health Research, Queens University Belfast, Belfast, UK

    • Frank Kee
  194. Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, Finland

    • Pirjo Komulainen
    • , Timo A. Lakka
    •  & Rainer Rauramaa
  195. Institute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio Campus, Kuopio, Finland

    • Pirjo Komulainen
    • , Timo A. Lakka
    •  & Rainer Rauramaa
  196. Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland

    • Pirjo Komulainen
    •  & Timo A. Lakka
  197. National Heart and Lung Institute, Imperial College London, Hammersmith Hospital Campus, London, UK

    • Jaspal S. Kooner
  198. MRC-PHE Centre for Environment and Health, Imperial College London, London, UK

    • Jaspal S. Kooner
  199. Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland

    • Tellervo Korhonen
  200. Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa

    • Helena Kuivaniemi
  201. Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa

    • Helena Kuivaniemi
    •  & Gerard Tromp
  202. Institute of Social and Preventive Medicine, Lausanne University Hospital, Lausanne, Switzerland

    • Zoltán Kutalik
  203. Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland

    • Johanna Kuusisto
    •  & Markku Laakso
  204. Department of Genetics, University of North Carolina, Chapel Hill, NC, USA

    • Ethan M. Lange
    • , Leslie A. Lange
    • , Karen L. Mohlke
    •  & Ying Wu
  205. Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA

    • Eric B. Larson
  206. Department of Health Services, University of Washington, Seattle, WA, USA

    • Eric B. Larson
  207. Department of Anthropology, Sociology and History, University of San Carlos, Cebu City, Philippines

    • Nanette R. Lee
  208. USC–Office of Population Studies Foundation, Inc., University of San Carlos, Cebu City, Philippines

    • Nanette R. Lee
  209. Division of Preventive Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

    • Cora E. Lewis
  210. Department of Medicine, Boston University School of Medicine, Boston, MA, USA

    • Honghuang Lin
  211. Department of Ophthalmology, Taichung Veterans General Hospital, Taichung, Taiwan

    • Keng-Hung Lin
  212. Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden

    • Lars Lind
  213. Department of Clinical Experimental Research, Rigshospitalet, Copenhagen, Denmark

    • Allan Linneberg
  214. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    • Allan Linneberg
  215. Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA

    • Ching-Ti Liu
    • , Gina M. Peloso
    •  & Shuai Wang
  216. Department of Public Health Sciences, Institute for Personalized Medicine, Pennsylvania State University College of Medicine, Hershey, PA, USA

    • Dajiang J. Liu
  217. Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA

    • Yongmei Liu
    •  & Lynne E. Wagenknecht
  218. Division of Health Sciences, Warwick Medical School, Warwick University, Coventry, UK

    • Artitaya Lophatananon
  219. Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA

    • Roberta McKean-Cowdin
  220. Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Nuthetal, Germany

    • Karina Meidtner
    •  & Matthias B. Schulze
  221. German Center for Diabetes Research, Neuherberg, Germany

    • Karina Meidtner
    • , Annette Peters
    •  & Matthias B. Schulze
  222. Westmead Millennium Institute of Medical Research, Centre for Vision Research and Department of Ophthalmology, University of Sydney, Sydney, New South Wales, Australia

    • Paul Mitchell
  223. Department of Medicine, Kuopio University Hospital, Kuopio, Finland

    • Leena Moilanen
  224. Department of Epidemiology and Public Health, University of Strasbourg, Strasbourg, France

    • Marie Moitry
  225. Department of Public Health, University Hospital of Strasbourg, Strasbourg, France

    • Marie Moitry
  226. Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia

    • Grant W. Montgomery
  227. Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, The Netherlands

    • Dennis O. Mook-Kanamori
  228. INTERVAL Coordinating Centre, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK

    • Carmel Moore
  229. School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia

    • Trevor A. Mori
  230. Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK

    • Andrew D. Morris
    • , Ozren Polasek
    •  & Igor Rudan
  231. Department of Medicine I, University Hospital Großhadern, Ludwig-Maximilians-Universitat, Munich, Germany

    • Martina Müller-Nurasyid
  232. German Centre for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany

    • Martina Müller-Nurasyid
    •  & Annette Peters
  233. Laboratory of Neurogenetics, National Institute on Aging, US National Institutes of Health, Bethesda, MD, USA

    • Mike A. Nalls
  234. Data Tecnica International, Glen Echo, MD, USA

    • Mike A. Nalls
  235. Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia

    • Dale R. Nyholt
  236. Program for Personalized and Genomic Medicine, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA

    • Jeffrey R. O’Connel
    • , James A. Perry
    •  & Laura M. Yerges-Armstrong
  237. Division of Cardiovascular Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    • Michelle L. O’Donoghue
    • , Paul M. Ridker
    •  & Hayato Tada
  238. Center for Neurobehavioral Genetics, University of California, Los Angeles, Los Angeles, CA, USA

    • Loes M. Olde Loohuis
    •  & Roel A. Ophoff
  239. Pat Macpherson Centre for Pharmacogenetics and Pharmacogenomics, Medical Research Institute, Ninewells Hospital and Medical School, Dundee, UK

    • Colin N. A. Palmer
  240. Laboratory of Clinical Chemistry and Hematology, Division of Laboratories and Pharmacy, University Medical Center Utrecht, Utrecht, The Netherlands

    • Gerard Pasterkamp
  241. School of Women’s and Infants’ Health, University of Western Australia, Perth, Western Australia, Australia

    • Craig E. Pennell
    •  & Carol A. Wang
  242. Diabetes and Obesity Research Program, University of Helsinki, Helsinki, Finland

    • Markus Perola
  243. Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark

    • Tune H. Pers
  244. Institute of Epidemiology II, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany

    • Annette Peters
  245. Department of Clinical Immunology and Biochemistry, Lillebaelt Hospital, Vejle, Denmark

    • Eva R. B. Petersen
  246. School of Medicine, University of Split, Split, Croatia

    • Ozren Polasek
  247. Central Hospital of Southern Ostrobothnia, Seinäjoki, Finland

    • Hannu Puolijoki
  248. Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland

    • Olli T. Raitakari
  249. Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland

    • Olli T. Raitakari
  250. Centre for Non-Communicable Diseases, Karachi, Pakistan

    • Asif Rasheed
    •  & Danish Saleheen
  251. Department of Biobank Research, Umeå University, Umeå, Sweden

    • Frida Renström
  252. Wellcome Trust Centre for Human Genetics, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK

    • Manuel A. Rivas
  253. NHS Blood and Transplant–Oxford Centre, Oxford, UK

    • David J. Roberts
  254. BRC Haematology Theme and Radcliffe Department of Medicine, University of Oxford, Oxford, UK

    • David J. Roberts
  255. Department of Public Health and Clinical Medicine, Unit of Family Medicine, Umeå University, Umeå, Sweden

    • Olov Rolandsson
  256. Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, UK

    • Katherine S. Ruth
    • , Andrew R. Wood
    • , Hanieh Yaghootkar
    •  & Timothy M. Frayling
  257. Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    • Danish Saleheen
    •  & Wei Zhao
  258. Departments of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    • Robert E. Schoen
  259. Duke Molecular Physiology Institute, Duke University, Durham, NC, USA

    • Svati H. Shah
  260. Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan

    • Wayne H.-H. Sheu
  261. School of Medicine, National Defense Medical Center, Taipei, Taiwan

    • Wayne H.-H. Sheu
  262. School of Medicine, National Yang-Ming University, Taipei, Taiwan

    • Wayne H.-H. Sheu
  263. Saw Swee Hock School of Public Health, National University Health System, National University of Singapore, Singapore, Singapore

    • Xueling Sim
  264. Genetics, Target Sciences, GlaxoSmithKline, Research Triangle Park, NC, USA

    • Andrew J. Slater
  265. OmicSoft at Qiagen Company, Cary, NC, USA

    • Andrew J. Slater
  266. Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK

    • Kerrin S. Small
    •  & Timothy D. Spector
  267. Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK

    • John M. Starr
  268. deCODE Genetics/Amgen, Inc., Reykjavik, Iceland

    • Kari Stefansson
    • , Valgerdur Steinthorsdottir
    • , Gudmar Thorleifsson
    •  & Unnur Thorsteinsdottir
  269. Chair of Genetic Epidemiology, IBE, Faculty of Medicine, LMU Munich, Munich, Germany

    • Konstantin Strauch
  270. Kanazawa University, Kanazawa, Japan

    • Hayato Tada
  271. College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK

    • Katherine E. Tansey
  272. Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany

    • Alexander Teumer
  273. Center for Pediatric Research, Department for Women’s and Child Health, University of Leipzig, Leipzig, Germany

    • Anke Tönjes
  274. Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands

    • Stella Trompet
  275. Anogia Medical Centre, Anogia, Greece

    • Emmanouil Tsafantakis
  276. Centre for Vascular Prevention, Danube University Krems, Krems, Austria

    • Jaakko Tuomilehto
  277. Dasman Diabetes Institute, Dasman, Kuwait

    • Jaakko Tuomilehto
  278. Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia

    • Jaakko Tuomilehto
  279. Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada

    • Rudolf Uher
  280. Department of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland

    • Matti Uusitupa
  281. Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands

    • Nienke Leeuwen
  282. Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands

    • Nienke Leeuwen
  283. Primary Health Care Unit, Central Hospital of Central Finland, Jyväskylä, Finland

    • Mauno Vanhala
  284. Primary Health Care Unit, Kuopio University Hospital, Kuopio, Finland

    • Mauno Vanhala
  285. USC Roski Eye Institute, Department of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA

    • Rohit Varma
  286. Department of Obstetrics and Gynecology, Institute for Medicine and Public Health, Vanderbilt Genetics Institute, Vanderbilt University, Nashville, TN, USA

    • Digna R. Velez Edwards
  287. Research Center on Epidemiology and Preventive Medicine, Department of Medicine and Surgery, University of Insubria, Varese, Italy

    • Giovanni Veronesi
  288. Cardiometabolic Disease, Merck, Sharp & Dohme, Kenilworth, NJ, USA

    • Thomas F. Vogt
  289. German Centre for Cardiovascular Research (DZHK), partner site Greifswald, Greifswald, Germany

    • Uwe Völker
  290. Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany

    • Uwe Völker
  291. Institute of Cellular Medicine, Medical School, Newcastle University, Newcastle, UK

    • Mark Walker
  292. Department of Medical Sciences, Cardiology, Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden

    • Lars Wallentin
  293. Genetics, Target Sciences, GlaxoSmithKline, King of Prussia, PA, USA

    • Dawn M. Waterworth
  294. Departments of Epidemiology and Medicine, Diabetes Translational Research Center, Fairbanks School of Public Health and School of Medicine, Indiana University, Indianapolis, IN, USA

    • Jennifer Wessel
  295. Green Lane Cardiovascular Service, Auckland City Hospital and University of Auckland, Auckland, New Zealand

    • Harvey D. White
  296. Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA

    • Cristen J. Willer
  297. Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA

    • James G. Wilson
  298. Danish Diabetes Academy, Odense, Denmark

    • Daniel R. Witte
  299. Department of Public Health, Aarhus University, Aarhus, Denmark

    • Daniel R. Witte
  300. GlaxoSmithKline, King of Prussia, PA, USA

    • Laura M. Yerges-Armstrong
  301. Department of Clinical Sciences, Quantitative Biomedical Research Center, Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX, USA

    • Xiaowei Zhan
  302. Endometriosis CaRe Centre, Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford, UK

    • Krina T Zondervan
  303. Department of Epidemiology and Carolina Center of Genome Sciences, Chapel Hill, NC, USA

    • Kari E. North
  304. Li Ka Shing Centre for Health Information and Discovery, Big Data Institute, University of Oxford, Oxford, UK

    • Cecilia M. Lindgren
  305. Department of Pediatrics, Harvard Medical School, Boston, MA, USA

    • Joel N. Hirschhorn
  306. Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    • Ruth J. F. Loos

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