作者
Richa Saxena,Benjamin F. Voight,Valeriya Lyssenko,Noël P. Burtt,Paul I. W. de Bakker,Hong Chen,Jeffrey J. Roix,Sekar Kathiresan,Joel N. Hirschhorn,Mark J. Daly,Thomas E. Hughes,Leif Groop,David Altshuler,Peter Almgren,José C. Florez,Joanne M. Meyer,Kristin Ardlie,Kristina Bengtsson Boström,Bo Isomaa,Guillaume Lettre,Ulf Lindblad,Helen N. Lyon,Olle Melander,Christopher Newton‐Cheh,Peter M. Nilsson,Marju Orho‐Melander,Lennart Råstam,Elizabeth K. Speliotes,Marja‐Riitta Taskinen,Jaakko Tuomilehto,Candace Guiducci,Anna Berglund,Joyce Carlson,Lauren Gianniny,Rachel Hackett,Liselotte Hall,Johan Holmkvist,Esa Laurila,Marketa Sjögren,Maria Sterner,Aarti Surti,Margareta Svensson,Malin Svensson,Ryan Tewhey,Brendan Blumenstiel,Melissa Parkin,Matthew DeFelice,Rachel Barry,Wendy Brodeur,Jody Camarata,Nancy Chia,Maurizio Fava,John G. Gibbons,B. Handsaker,Claire M. Healy,Christine Nguyen,Casey Gates,Carrie Sougnez,Diane Gage,Marcia M. Nizzari,Stacey Gabriel,Gung‐Wei Chirn,Qicheng Ma,Hemang Parikh,Delwood Richardson,Darrell Ricke,Shaun Purcell
摘要
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.