Genome-Wide Association Analysis Identifies Loci for Type 2 Diabetes and Triglyceride Levels

✍ Scribed by Saxena, R.; Voight, B. F.; Lyssenko, V.; Burtt, N. P.; de Bakker, P. I. W.; Chen, H.; Roix, J. J.; Kathiresan, S.; Hirschhorn, J. N.; Daly, M. J.; Hughes, T. E.; Groop, L.; Altshuler, D.; Almgren, P.; Florez, J. C.; Meyer, J.; Ardlie, K.; Bengtsson Bostrom, K.; Isomaa, B.; Lettre, G.; Lindblad, U.; Lyon, H. N.; Melander, O.; Newton-Cheh, C.; Nilsson, P.; Orho-Melander, M.; Rastam, L.; Speliotes, E. K.; Taskinen, M.-R.; Tuomi, T.; Guiducci, C.; Berglund, A.; Carlson, J.; Gianniny, L.; Hackett, R.; Hall, L.; Holmkvist, J.; Laurila, E.; Sjogren, M.; Sterner, M.; Surti, A.; Svensson, M.; Svensson, M.; Tewhey, R.; Blumenstiel, B.; Parkin, M.; DeFelice, M.; Barry, R.; Brodeur, W.; Camarata, J.; Chia, N.; Fava, M.; Gibbons, J.; Handsaker, B.; Healy, C.; Nguyen, K.; Gates, C.; Sougnez, C.; Gage, D.; Nizzari, M.; Gabriel, S. B.; Chirn, G.-W.; Ma, Q.; Parikh, H.; Richardson, D.; Ricke, D.; Purcell, S.

• Book ID: 118268358
• Publisher: American Association for the Advancement of Science
• Year: 2007
• Tongue: English
• Weight: 444 KB
• Volume: 316
• Category: Article
• ISSN: 0036-8075
• DOI: 10.1126/science.1142358

✦ Synopsis

New strategies for prevention and treatment of type 2 diabetes (T2D) require improved insight into disease etiology. We analyzed 386,731 common single-nucleotide polymorphisms (SNPs) in 1464 patients with T2D and 1467 matched controls, each characterized for measures of glucose metabolism, lipids, obesity, and blood pressure. With collaborators (FUSION and WTCCC/UKT2D), we identified and confirmed three loci associated with T2D—in a noncoding region near
CDKN2A
and
CDKN2B
, in an intron of
IGF2BP2
, and an intron of
CDKAL1
—and replicated associations near
HHEX
and in
SLC30A8
found by a recent whole-genome association study. We identified and confirmed association of a SNP in an intron of glucokinase regulatory protein (GCKR) with serum triglycerides. The discovery of associated variants in unsuspected genes and outside coding regions illustrates the ability of genome-wide association studies to provide potentially important clues to the pathogenesis of common diseases.