Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels by Diabetes Genetics Initiative of Broad Institute of Harvard and MIT, Lund University, and Novartis Institutes of BioMedical Research, Saxena Richa, Voight Benjamin F, Lyssenko Valeriya, Burtt Noël P, de Bakker Paul I W, Chen Hong, Roix Jeffrey J, Kathiresan Sekar, Hirschhorn Joel N, Daly Mark J, Hughes Thomas E, Groop Leif, Altshuler David, Almgren Peter, Florez Jose C, Meyer Joanne, Ardlie Kristin, Bengtsson Boström Kristina, Isomaa Bo, Lettre Guillaume, Lindblad Ulf, Lyon Helen N, Melander Olle, Newton-Cheh Christopher, Nilsson Peter, Orho-Melander Marju, Råstam Lennart, Speliotes Elizabeth K, Taskinen Marja-Riitta, Tuomi Tiinamaija, Guiducci Candace, Berglund Anna, Carlson Joyce, Gianniny Lauren, Hackett Rachel, Hall Liselotte, Holmkvist Johan, Laurila Esa, Sjögren Marketa, Sterner Maria, Surti Aarti, Svensson Margareta, Svensson Malin, Tewhey Ryan, Blumenstiel Brendan, Parkin Melissa, Defelice Matthew, Barry Rachel, Brodeur Wendy, Camarata Jody, Chia Nancy, Fava Mary, Gibbons John, Handsaker Bob, Healy Claire, Nguyen Kieu, Gates Casey, Sougnez Carrie, Gage Diane, Nizzari Marcia, Gabriel Stacey B, Chirn Gung-Wei, Ma Qicheng, Parikh Hemang, Richardson Delwood, Ricke Darrell, Purcell Shaun in Science (New York, N.Y.) (2007). PubMed

Abstract

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.

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