Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels.
Diabetes Genetics Initiative of Broad Institute of Harvard and MIT, Lund University, and 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,
Hackett R,
Hall L,
Holmkvist J,
Laurila E,
Sjögren 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 SB,
Chirn GW,
Ma Q,
Parikh H,
Richardson D,
Ricke D,
Purcell S.
Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, MA 02142, USA.
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.
PMID: 17463246 [PubMed - indexed for MEDLINE]