A Genome-Wide Association Study of Type 2 Diabetes in Finns Detects Multiple Susceptibility Variants

Laura J. Scott(University of North Carolina at Chapel Hill), Karen L. Mohlke(University of North Carolina at Chapel Hill), Lori L. Bonnycastle(University of North Carolina at Chapel Hill), Cristen J. Willer(University of North Carolina at Chapel Hill), Yun Li(University of North Carolina at Chapel Hill), William L. Duren(University of North Carolina at Chapel Hill), Michael R. Erdos(University of North Carolina at Chapel Hill), Heather M. Stringham(University of North Carolina at Chapel Hill), Peter S. Chines(University of North Carolina at Chapel Hill), Anne Jackson(University of North Carolina at Chapel Hill), Ludmila Prokunina‐Olsson(University of North Carolina at Chapel Hill), Chia-Jen Ding(University of North Carolina at Chapel Hill), Amy J. Swift(University of North Carolina at Chapel Hill), Narisu Narisu(University of North Carolina at Chapel Hill), Tianle Hu(University of North Carolina at Chapel Hill), Randall Pruim(University of North Carolina at Chapel Hill), Rui Xiao(University of North Carolina at Chapel Hill), Xiaoyi Li(University of North Carolina at Chapel Hill), Karen N. Conneely(University of North Carolina at Chapel Hill), Nancy L. Riebow(University of North Carolina at Chapel Hill), Andrew G. Sprau(University of North Carolina at Chapel Hill), Maurine Tong(University of North Carolina at Chapel Hill), Peggy P. White(University of North Carolina at Chapel Hill), Kurt N. Hetrick(University of North Carolina at Chapel Hill), Michael W. Barnhart(University of North Carolina at Chapel Hill), Craig W. Bark(University of North Carolina at Chapel Hill), Janet L. Goldstein(University of North Carolina at Chapel Hill), Lee Watkins(University of North Carolina at Chapel Hill), Xiang Fang(University of North Carolina at Chapel Hill), Jouko Saramies(University of North Carolina at Chapel Hill), Thomas A. Buchanan(University of North Carolina at Chapel Hill), Richard M. Watanabe(University of North Carolina at Chapel Hill), Timo T. Valle(University of North Carolina at Chapel Hill), Leena Kinnunen(University of North Carolina at Chapel Hill), Gonçalo R. Abecasis(University of North Carolina at Chapel Hill), Elizabeth Pugh(University of North Carolina at Chapel Hill), Kimberly F. Doheny(University of North Carolina at Chapel Hill), Richard N. Bergman(University of North Carolina at Chapel Hill), Jaakko Tuomilehto(University of North Carolina at Chapel Hill), Francis S. Collins(University of North Carolina at Chapel Hill), Michael Boehnke(University of North Carolina at Chapel Hill)
Science
April 26, 2007
10.1126/science.1142382
Cited by 2,774

Abstract

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.

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