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Science DOI:10.1126/science.1142358

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

Publication TypeJournal Article
Year of Publication2007
AuthorsSaxena, R, Voight, BF, Lyssenko, V, Burtt, NP, de Bakker, PIW, Chen, H, Roix, JJ, Kathiresan, S, Hirschhorn, JN, Daly, MJ, Hughes, TE, Groop, L, Altshuler, D, Almgren, P, Florez, JC, Meyer, J, Ardlie, K, Boström, KBengtsson, Isomaa, B, Lettre, G, Lindblad, U, Lyon, HN, Melander, O, Newton-Cheh, C, Nilsson, P, Orho-Melander, M, Råstam, L, Speliotes, EK, Taskinen, M-R, 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, G-W, Ma, Q, Parikh, H, Richardson, D, Ricke, D, Purcell, S
Corporate AuthorsDiabetes Genetics Initiative of Broad Institute of Harvard and MIT, Lund University, and Novartis Institutes of BioMedical Research
JournalScience
Volume316
Issue5829
Pages1331-6
Date Published2007 Jun 01
ISSN1095-9203
KeywordsAdaptor Proteins, Signal Transducing, Aged, Alleles, Blood Glucose, Case-Control Studies, Chromosome Mapping, Chromosomes, Human, Pair 9, Diabetes Mellitus, Type 2, Female, Genetic Markers, Genetic Predisposition to Disease, Genome, Human, Genotype, Haplotypes, Humans, Insulin Resistance, Insulin-Like Growth Factor Binding Proteins, Introns, Male, Meta-Analysis as Topic, Middle Aged, Polymorphism, Single Nucleotide, Quantitative Trait, Heritable, Triglycerides
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.

URLhttp://www.sciencemag.org/cgi/pmidlookup?view=short&pmid=17463246
DOI10.1126/science.1142358
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/17463246?dopt=Abstract

Alternate JournalScience
PubMed ID17463246
Grant ListK23 DK65978-04 / DK / NIDDK NIH HHS / United States
K23 DK080145 / DK / NIDDK NIH HHS / United States
K23 DK080145-01 / DK / NIDDK NIH HHS / United States
U01 HG004171 / HG / NHGRI NIH HHS / United States
K23-HL083102 / HL / NHLBI NIH HHS / United States
F32 DK079466 / DK / NIDDK NIH HHS / United States
F32 DK079466-01 / DK / NIDDK NIH HHS / United States
K23 DK067288 / DK / NIDDK NIH HHS / United States