全基因组关联分析确定2型糖尿病和甘油三酯水平的基因座。
Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels.
作者信息
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
机构信息
Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, MA 02142, USA.
出版信息
Science. 2007 Jun 1;316(5829):1331-6. doi: 10.1126/science.1142358. Epub 2007 Apr 26.
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.
2型糖尿病（T2D）预防和治疗的新策略需要深入了解疾病病因。我们分析了1464例T2D患者和1467例匹配对照中的386,731个常见单核苷酸多态性（SNP），每例均具有葡萄糖代谢、脂质、肥胖和血压测量特征。与合作者（FUSION和WTCCC/UKT2D）一起，我们鉴定并确认了三个与T2D相关的基因座——在CDKN2A和CDKN2B附近的一个非编码区域、IGF2BP2的一个内含子以及CDKAL1的一个内含子中——并重复了最近一项全基因组关联研究发现的HHEX附近和SLC30A8中的关联。我们鉴定并确认了葡萄糖激酶调节蛋白（GCKR）内含子中的一个SNP与血清甘油三酯的关联。在未被怀疑的基因和编码区域之外发现相关变异，说明了全基因组关联研究为常见疾病发病机制提供潜在重要线索的能力。
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