Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels.

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.
Authors	Diabetes Genetics Initiative of Broad Institute of Harvard and MIT, Lund University, and Novartis Institutes of BioMedical Research, 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, Jose C Florez, Joanne Meyer, Kristin Ardlie, Kristina Bengtsson Boström, Bo Isomaa, Guillaume Lettre, Ulf Lindblad, Helen N Lyon, Olle Melander, Christopher Newton-Cheh, Peter Nilsson, Marju Orho-Melander, Lennart Råstam, Elizabeth K Speliotes, Marja-Riitta Taskinen, Tiinamaija Tuomi, 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, Mary Fava, John Gibbons, Bob Handsaker, Claire Healy, Kieu Nguyen, Casey Gates, Carrie Sougnez, Diane Gage, Marcia Nizzari, Stacey B Gabriel, Gung-Wei Chirn, Qicheng Ma, Hemang Parikh, Delwood Richardson, Darrell Ricke, Shaun Purcell
Journal	Science (New York, N.Y.) (Science) Vol. 316 Issue 5829 Pg. 1331-6 (Jun 01 2007) ISSN: 1095-9203 [Electronic] United States
PMID	17463246 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Adaptor Proteins, Signal Transducing Blood Glucose GCKR protein, human Genetic Markers Insulin-Like Growth Factor Binding Proteins Triglycerides
Topics	Adaptor Proteins, Signal Transducing (genetics) Aged Alleles Blood Glucose (analysis) Case-Control Studies Chromosome Mapping Chromosomes, Human, Pair 9 (genetics) Diabetes Mellitus, Type 2 (genetics) Female Genetic Markers Genetic Predisposition to Disease Genome, Human Genotype Haplotypes Humans Insulin Resistance (genetics) Insulin-Like Growth Factor Binding Proteins (genetics) Introns Male Meta-Analysis as Topic Middle Aged Polymorphism, Single Nucleotide Quantitative Trait, Heritable Triglycerides (blood)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!