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

Laura J. Scott, Karen L. Mohlke, Lori L. Bonnycastle, Cristen J. Willer, Yun Li, William L. Duren, Michael R. Erdos, Heather M. Stringham, Peter S. Chines, Anne U. Jackson, Ludmila Prokunina-Olsson, Chia Jen Ding, Amy J. Swift, Narisu, Tianle Hu, Randall Pruim, Rui Xiao, Xiao Yi Li, Karen N. Conneely, Nancy L. RiebowAndrew G. Sprau, Maurine Tong, Peggy P. White, Kurt N. Hetrick, Michael W. Barnhart, Craig W. Bark, Janet L. Goldstein, Lee Watkins, Fang Xiang, Jouko Saramies, Thomas A. Buchanan, Richard M. Watanabe, Timo T. Valle, Leena Kinnunen, Gonçalo R. Abecasis, Elizabeth W. Pugh, Kimberly F. Doheny, Richard N. Bergman, Jaakko Tuomilehto, Francis S. Collins, Michael Boehnke

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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.

Original languageEnglish (US)
Pages (from-to)1341-1345
Number of pages5
JournalScience
Volume316
Issue number5829
DOIs
StatePublished - Jun 1 2007

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ASJC Scopus subject areas

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Scott, L. J., Mohlke, K. L., Bonnycastle, L. L., Willer, C. J., Li, Y., Duren, W. L., Erdos, M. R., Stringham, H. M., Chines, P. S., Jackson, A. U., Prokunina-Olsson, L., Ding, C. J., Swift, A. J., Narisu, Hu, T., Pruim, R., Xiao, R., Li, X. Y., Conneely, K. N., ... Boehnke, M. (2007). A genome-wide association study of type 2 diabetes in finns detects multiple susceptibility variants. Science, 316(5829), 1341-1345. https://doi.org/10.1126/science.1142382