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Comprehensive association study of type 2 diabetes and related quantitative traits with 222 candidate genes.

ABSTRACT: Type 2 diabetes is a common complex disorder with environmental and genetic components. We used a candidate gene-based approach to identify single nucleotide polymorphism (SNP) variants in 222 candidate genes that influence susceptibility to type 2 diabetes.In a case-control study of 1,161 type 2 diabetic subjects and 1,174 control Finns who are normal glucose tolerant, we genotyped 3,531 tagSNPs and annotation-based SNPs and imputed an additional 7,498 SNPs, providing 99.9% coverage of common HapMap variants in the 222 candidate genes. Selected SNPs were genotyped in an additional 1,211 type 2 diabetic case subjects and 1,259 control subjects who are normal glucose tolerant, also from Finland.Using SNP- and gene-based analysis methods, we replicated previously reported SNP-type 2 diabetes associations in PPARG, KCNJ11, and SLC2A2; identified significant SNPs in genes with previously reported associations (ENPP1 [rs2021966, P = 0.00026] and NRF1 [rs1882095, P = 0.00096]); and implicated novel genes, including RAPGEF1 (rs4740283, P = 0.00013) and TP53 (rs1042522, Arg72Pro, P = 0.00086), in type 2 diabetes susceptibility.Our study provides an effective gene-based approach to association study design and analysis. One or more of the newly implicated genes may contribute to type 2 diabetes pathogenesis. Analysis of additional samples will be necessary to determine their effect on susceptibility.

SUBMITTER: Gaulton KJ

PROVIDER: S-EPMC2570412 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature

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Comprehensive association study of type 2 diabetes and related quantitative traits with 222 candidate genes.

Gaulton Kyle J KJ Willer Cristen J CJ Li Yun Y Scott Laura J LJ Conneely Karen N KN Jackson Anne U AU Duren William L WL Chines Peter S PS Narisu Narisu N Bonnycastle Lori L LL Luo Jingchun J Tong Maurine M Sprau Andrew G AG Pugh Elizabeth W EW Doheny Kimberly F KF Valle Timo T TT Abecasis Gonçalo R GR Tuomilehto Jaakko J Bergman Richard N RN Collins Francis S FS Boehnke Michael M Mohlke Karen L KL

Diabetes 20080804 11

<h4>Objective</h4>Type 2 diabetes is a common complex disorder with environmental and genetic components. We used a candidate gene-based approach to identify single nucleotide polymorphism (SNP) variants in 222 candidate genes that influence susceptibility to type 2 diabetes.<h4>Research design and methods</h4>In a case-control study of 1,161 type 2 diabetic subjects and 1,174 control Finns who are normal glucose tolerant, we genotyped 3,531 tagSNPs and annotation-based SNPs and imputed an addit ...[more]

PMID: 18678618

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Comprehensive association study of type 2 diabetes and related quantitative traits with 222 candidate genes.

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Comprehensive association study of type 2 diabetes and related quantitative traits with 222 candidate genes.

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