Genome-Wide Association Analysis Identifies Loci for Type 2 Diabetes and Triglyceride Levels

Richa Saxena(Broad Institute), Benjamin F. Voight(Broad Institute), Valeriya Lyssenko(Broad Institute), Noël P. Burtt(Broad Institute), Paul I. W. de Bakker(Broad Institute), Hong Chen(Broad Institute), Jeffrey J. Roix(Broad Institute), Sekar Kathiresan(Broad Institute), Joel N. Hirschhorn(Broad Institute), Mark J. Daly(Broad Institute), Thomas E. Hughes(Broad Institute), Leif Groop(Broad Institute), David Altshuler(Broad Institute), Peter Almgren(Broad Institute), José C. Florez(Broad Institute), Joanne M. Meyer(Broad Institute), Kristin Ardlie(Broad Institute), Kristina Bengtsson Boström(Broad Institute), Bo Isomaa(Broad Institute), Guillaume Lettre(Broad Institute), Ulf Lindblad(Broad Institute), Helen N. Lyon(Broad Institute), Olle Melander(Broad Institute), Christopher Newton‐Cheh(Broad Institute), Peter M. Nilsson(Broad Institute), Marju Orho‐Melander(Broad Institute), Lennart Råstam(Broad Institute), Elizabeth K. Speliotes(Broad Institute), Marja‐Riitta Taskinen(Broad Institute), Tiinamaija Tuomi(Broad Institute), Candace Guiducci(Broad Institute), Anna Berglund(Broad Institute), Joyce Carlson(Broad Institute), Lauren Gianniny(Broad Institute), Rachel Hackett(Broad Institute), Liselotte Hall(Broad Institute), Johan Holmkvist(Broad Institute), Esa Laurila(Broad Institute), Marketa Sjögren(Broad Institute), Maria Sterner(Broad Institute), Aarti Surti(Broad Institute), Margareta Svensson(Broad Institute), Malin Svensson(Broad Institute), Ryan Tewhey(Broad Institute), Brendan Blumenstiel(Broad Institute), Melissa Parkin(Broad Institute), Matthew DeFelice(Broad Institute), Rachel Barry(Broad Institute), Wendy Brodeur(Broad Institute), Jody Camarata(Broad Institute), Nancy Chia(Broad Institute), Mary Fava(Broad Institute), John G. Gibbons(Broad Institute), B. Handsaker(Broad Institute), Claire M. Healy(Broad Institute), Christine Nguyen(Broad Institute), Casey Gates(Broad Institute), Carrie Sougnez(Broad Institute), Diane Gage(Broad Institute), Marcia M. Nizzari(Broad Institute), Stacey Gabriel(Broad Institute), Gung‐Wei Chirn(Broad Institute), Qicheng Ma(Broad Institute), Hemang Parikh(Broad Institute), Delwood Richardson(Broad Institute), Darrell Ricke(Broad Institute), Shaun Purcell(Broad Institute)
Science
April 26, 2007
10.1126/science.1142358
Cited by 2,887

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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