학술논문
Comprehensive Association Study of Type 2 Diabetes and Related Quantitative Traits With 222 Candidate Genes
Document Type
article
Author
Gaulton, Kyle J; Willer, Cristen J; Li, Yun; Scott, Laura J; Conneely, Karen N; Jackson, Anne U; Duren, William L; Chines, Peter S; Narisu, Narisu; Bonnycastle, Lori L; Luo, Jingchun; Tong, Maurine; Sprau, Andrew G; Pugh, Elizabeth W; Doheny, Kimberly F; Valle, Timo T; Abecasis, Gonçalo R; Tuomilehto, Jaakko; Bergman, Richard N; Collins, Francis S; Boehnke, Michael; Mohlke, Karen L
Source
Diabetes. 57(11)
Subject
Language
Abstract
ObjectiveType 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.Research design and methodsIn 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.ResultsUsing 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.ConclusionsOur 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.