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Diabetes Genetics Initiative of Broad Institute of Harvard MIT Lund University Novartis Institutes of BioMedical Research Saxena R Voight BF Lyssenko V Burtt NP de Bakker PI Chen H Roix JJ Kathiresan S Hirschhorn JN Daly MJ Hughes TE Groop L Altshuler D Almgren P Florez JC Meyer J Ardlie K Bengtsson Boström K Isomaa B Lettre G Lindblad U Lyon HN Melander O Newton-Cheh C Nilsson P Orho-Melander M Råstam L Speliotes EK Taskinen MR Tuomi T Guiducci C Berglund A Carlson J Gianniny L 《Science (New York, N.Y.)》2007,316(5829):1331-1336
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. 相似文献
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