A Genome-Wide Association Study of Type 2 Diabetes in Finns Detects Multiple Susceptibility Variants
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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We thank the Finnish citizens who generously participated in this study; our colleagues from the DGI, WTCCC, and UKT2D for sharing prepublication data from their studies; S. Enloe of FUSION and E. Kwasnik, J. Gearhart, J. Romm, M. Zilka, C. Ongaco, A. Robinson, R. King, B. Craig, and E. Hsu of CIDR for expert technical work; and D. Leja of NHGRI for expert assistance with a figure. Support for this research was provided by NIH grants DK062370 (M.B.), DK072193 (K.L.M.), HL084729 (G.R.A.), HG002651 (G.R.A.), and U54 DA021519; National Human Genome Research Institute intramural project number 1 Z01 HG000024 (F.S.C.); a postdoctoral fellowship award from the American Diabetes Association (C.J.W.); a Wenner-Gren Fellowship (L.P.O.); and a Calvin Research Fellowship (R.P.). Genome-wide genotyping was performed by the Johns Hopkins University Genetic Resources Core Facility (GRCF) SNP Center at CIDR with support from CIDR NIH (contract N01-HG-65403) and the GRCF SNP Center.
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Science
Volume 316 | Issue 5829
1 June 2007
1 June 2007
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American Association for the Advancement of Science.
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Received: 12 March 2007
Accepted: 20 April 2007
Published in print: 1 June 2007
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