期刊
HUMAN MOLECULAR GENETICS
卷 19, 期 13, 页码 2706-2715出版社
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddq156
关键词
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资金
- Gene Environment-Association Studies (GENEVA) under the NIH Genes, Environment and Health Initiative (GEI) [U01HG004738, U01HG004422, U01HG004402, U01HG0047 29, U01HG004726, U01HG004735, U01HG004415, U01HG0 04436, U01HG004423, U01HG004728, RFAHG006033]
- NIH (NIDCR) [U01DE018 993, U01DE018903]
- NIH, NIAAA [U10AA008401]
- NIH, NIDA [P01CA 089392, R01DA013423]
- NIH, NCI [CA63464, CA54281, CA1367 92, Z01CP010200]
- NIH GEI [U01HG04424, U01HG004438]
- NIH [HHSN268200782096C, HHSN268200625226C, UL1RR025005, RO1 HL71981, R01DK075046, R90DK071507]
- National Cancer Institute (NCI) [P01CA087969, P01CA055075, CA047988]
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R01DK058845, R01DK078616, K24 DK080140, K23 DK65978]
- National Heart, Lung, and Blood Institute (NHLBI) [HL043851, HL69757, N01-HC-55015, N01-HC-55016, N01-HC55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01HC- 55022, R01HL087641, R01HL59367, R01HL086694]
- Donald W. Reynolds Foundation
- Fondation Leducq
- Amgen
- NIH Roadmap for Medical Research
- NHLBI's Framingham Heart Study [N01-HC-25195]
- Affymetrix, Inc. [N02-HL-6-4278]
- Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center
- Massachusetts General Hospital
- Doris Duke Charitable Foundation
- American Heart Association
- Boston Obesity Nutrition Research Center [DK46200]
- Canadian Institutes of Health Research
- [K01DK067207]
To identify type 2 diabetes (T2D) susceptibility loci, we conducted genome-wide association (GWA) scans in nested case-control samples from two prospective cohort studies, including 2591 patients and 3052 controls of European ancestry. Validation was performed in 11 independent GWA studies of 10 870 cases and 73 735 controls. We identified significantly associated variants near RBMS1 and ITGB6 genes at 2q24, best-represented by SNP rs7593730 (combined OR = 0.90, 95% CI = 0.86-0.93; P = 3.7 x 10(-8)). The frequency of the risk-lowering allele T is 0.23. Variants in this region were nominally related to lower fasting glucose and HOMA-IR in the MAGIC consortium (P < 0.05). These data suggest that the 2q24 locus may influence the T2D risk by affecting glucose metabolism and insulin resistance.
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