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Originally published in Science Express on 26 April 2007
Science 1 June 2007:
Vol. 316. no. 5829, pp. 1341 - 1345
DOI: 10.1126/science.1142382
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Reports

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

Laura J. Scott,1 Karen L. Mohlke,2 Lori L. Bonnycastle,3 Cristen J. Willer,1 Yun Li,1 William L. Duren,1 Michael R. Erdos,3 Heather M. Stringham,1 Peter S. Chines,3 Anne U. Jackson,1 Ludmila Prokunina-Olsson,3 Chia-Jen Ding,1 Amy J. Swift,3 Narisu Narisu,3 Tianle Hu,1 Randall Pruim,4 Rui Xiao,1 Xiao-Yi Li,1 Karen N. Conneely,1 Nancy L. Riebow,3 Andrew G. Sprau,3 Maurine Tong,3 Peggy P. White,1 Kurt N. Hetrick,5 Michael W. Barnhart,5 Craig W. Bark,5 Janet L. Goldstein,5 Lee Watkins,5 Fang Xiang,1 Jouko Saramies,6 Thomas A. Buchanan,7 Richard M. Watanabe,8,9 Timo T. Valle,10 Leena Kinnunen,10,11 Gonçalo R. Abecasis,1 Elizabeth W. Pugh,5 Kimberly F. Doheny,5 Richard N. Bergman,9 Jaakko Tuomilehto,10,11,12 Francis S. Collins,3* Michael Boehnke1*

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.

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.
6 Savitaipale Health Center, 54800 Savitaipale, Finland.
7 Division of Endocrinology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
8 Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
9 Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
10 Diabetes Unit, Department of Epidemiology and Health Promotion, National Public Health Institute, 00300 Helsinki, Finland.
11 Department of Public Health, University of Helsinki, 00014 Helsinki, Finland.
12 South Ostrobothnia Central Hospital, 60220 Seinäjoki, Finland.

* To whom correspondence should be addressed. E-mail: boehnke{at}umich.edu (M.B.); francisc{at}mail.nih.gov (F.S.C.)

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