The genetic architecture of type 2 diabetes

C Fuchsberger; J Flannick; TM Teslovich; A Mahajan; V Agarwala; KJ Gaulton; C Ma; P Fontanillas; L Moutsianas; DJ McCarthy; MA Rivas; JRB Perry; X Sim; TW Blackwell; NR Robertson; NW Rayner; P Cingolani; AE Locke; JF Tajes; HM Highland; J Dupuis; PS Chines; CM Lindgren; C Hartl; AU Jackson; H Chen; JR Huyghe; M Van De Bunt; RD Pearson; A Kumar; M Müller-Nurasyid; N Grarup; HM Stringham; ER Gamazon; J Lee; Y Chen; RA Scott; JE Below; P Chen; J Huang; MJ Go; ML Stitzel; D Pasko; SCJ Parker; TV Varga; T Green; NL Beer; AG Day-Williams; T Ferreira; T Fingerlin; M Horikoshi; C Hu; I Huh; MK Ikram; BJ Kim; Y Kim; YJ Kim; MS Kwon; J Lee; S Lee; KH Lin; TJ Maxwell; Y Nagai; X Wang; RP Welch; J Yoon; W Zhang; N Barzilai; BF Voight; BG Han; CP Jenkinson; T Kuulasmaa; J Kuusisto; A Manning; MCY Ng; ND Palmer; B Balkau; A Stančáková; HE Abboud; H Boeing; V Giedraitis; D Prabhakaran; O Gottesman; J Scott; J Carey; P Kwan; G Grant; JD Smith; BM Neale; S Purcell; AS Butterworth; JMM Howson; HM Lee; Y Lu; SH Kwak; W Zhao; J Danesh; VKL Lam; KS Park; D Saleheen

Journal article

The genetic architecture of type 2 diabetes

C Fuchsberger, J Flannick, TM Teslovich, A Mahajan, V Agarwala, KJ Gaulton, C Ma, P Fontanillas, L Moutsianas, DJ McCarthy, MA Rivas, JRB Perry, X Sim, TW Blackwell, NR Robertson, NW Rayner, P Cingolani, AE Locke, JF Tajes, HM Highland Show all

Nature | NATURE PORTFOLIO | Published : 2016

DOI: 10.1038/nature18642

Abstract

The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sa..

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