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

Author:

Scott Laura J.12345,Mohlke Karen L.12345,Bonnycastle Lori L.12345,Willer Cristen J.12345,Li Yun12345,Duren William L.12345,Erdos Michael R.12345,Stringham Heather M.12345,Chines Peter S.12345,Jackson Anne U.12345,Prokunina-Olsson Ludmila12345,Ding Chia-Jen12345,Swift Amy J.12345,Narisu Narisu12345,Hu Tianle12345,Pruim Randall12345,Xiao Rui12345,Li Xiao-Yi12345,Conneely Karen N.12345,Riebow Nancy L.12345,Sprau Andrew G.12345,Tong Maurine12345,White Peggy P.12345,Hetrick Kurt N.12345,Barnhart Michael W.12345,Bark Craig W.12345,Goldstein Janet L.12345,Watkins Lee12345,Xiang Fang12345,Saramies Jouko12345,Buchanan Thomas A.12345,Watanabe Richard M.12345,Valle Timo T.12345,Kinnunen Leena12345,Abecasis Gonçalo R.12345,Pugh Elizabeth W.12345,Doheny Kimberly F.12345,Bergman Richard N.12345,Tuomilehto Jaakko12345,Collins Francis S.12345,Boehnke Michael12345

Affiliation:

1. Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.

2. Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.

3. Genome Technology Branch, National Human Genome Research Institute, Bethesda, MD 20892, USA.

4. Department of Mathematics and Statistics, Calvin College, Grand Rapids, MI 49546, USA.

5. Center for Inherited Disease Research (CIDR), Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21224, USA.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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