A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants

被引：2114

作者：

Scott, Laura J.

Mohlke, Karen L.

Bonnycastle, Lori L.

Willer, Cristen J.

Li, Yun

Duren, William L.

Erdos, Michael R.

Stringham, Heather M.

Chines, Peter S.

Jackson, Anne U.

Prokunina-Olsson, Ludmila

Ding, Chia-Jen

Swift, Amy J.

Narisu, Narisu

Hu, Tianle

Pruim, Randall

Xiao, Rui

Li, Xiao-Yi

Conneely, Karen N.

Riebow, Nancy L.

Sprau, Andrew G.

Tong, Maurine

White, Peggy P.

Hetrick, Kurt N.

Barnhart, Michael W.

Bark, Craig W.

Goldstein, Janet L.

Watkins, Lee

Xiang, Fang

Saramies, Jouko

Buchanan, Thomas A.

Watanabe, Richard M.

Valle, Timo T.

Kinnunen, Leena

Abecasis, Gonalo R.

Pugh, Elizabeth W.

Doheny, Kimberly F.

Bergman, Richard N.

Tuomilehto, Jaakko

Collins, Francis S.

Boehnke, Michael ^{[1
]}

机构：

[1] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Ctr State Genet, Ann Arbor, MI 48109 USA

[3] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA

[4] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA

[5] Calvin Coll, Dept Math & Stat, Grand Rapids, MI 49546 USA

[6] Johns Hopkins Univ, Sch Med, Inst Med Genet, Ctr Inherited Dis Res, Baltimore, MD 21224 USA

[7] Savitaipale Hlth Ctr, Savitaipate 54800, Finland

[8] Univ So Calif, Keck Sch Med, Div Endocrinol, Los Angeles, CA 90033 USA

[9] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA

[10] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA

[11] Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Diabet Unit, SF-00300 Helsinki, Finland

[12] Univ Helsinki, Dept Publ Hlth, Helsinki 00014, Finland

[13] S Ostrobothnia Cent Hosp, Seinajoki 60220, Finland

来源：

SCIENCE | 2007年 / 316卷 / 5829期

关键词：

D O I：

10.1126/science.1142382

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Identifying the genetic variants that increase the risk of type 2 diabetes (T2D) in humans has been a formidable challenge. Adopting a genome-wide association strategy, we genotyped 1161 Finnish T2D cases and 1174 Finnish normal glucose tolerant (NGT) controls with >315,000 single-nucleotide polymorphisms (SNPs) and imputed genotypes for an additional >2 million autosomal SNPs. We carried out association analysis with these SNPs to identify genetic variants that predispose to T2D, compared our T2D association results with the results of two similar studies, and genotyped 80 SNPs in an additional 1215 Finnish T2D cases and 1258 Finnish NGT controls. We identify T2D-associated variants in an intergenic region of chromosome 11p12, contribute to the identification of T2D-associated variants near the genes IGF2BP2 and CDKAL1 and the region of CDKN2A and CDKN2B, and confirm that variants near TCF7L2, SLC30A8, HHEX, FTO, PPARG, and KCNJ11 are associated with T2D risk. This brings the number of T2D loci now confidently identified to at least 10.

引用

页码：1341 / 1345

页数：5

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