title: A genome-wide association study identifies susceptibility variants for type 2 diabetes in Han Chinese.
abstract: To investigate the underlying mechanisms of T2D pathogenesis, we looked for diabetes susceptibility genes that increase the risk of type 2 diabetes (T2D) in a Han Chinese population. A two-stage genome-wide association (GWA) study was conducted, in which 995 patients and 894 controls were genotyped using the Illumina HumanHap550-Duo BeadChip for the first genome scan stage. This was further replicated in 1,803 patients and 1,473 controls in stage 2. We found two loci not previously associated with diabetes susceptibility in and around the genes protein tyrosine phosphatase receptor type D (PTPRD) (P = 8.54x10(-10); odds ratio [OR] = 1.57; 95% confidence interval [CI] = 1.36-1.82), and serine racemase (SRR) (P = 3.06x10(-9); OR = 1.28; 95% CI = 1.18-1.39). We also confirmed that variants in KCNQ1 were associated with T2D risk, with the strongest signal at rs2237895 (P = 9.65x10(-10); OR = 1.29, 95% CI = 1.19-1.40). By identifying two novel genetic susceptibility loci in a Han Chinese population and confirming the involvement of KCNQ1, which was previously reported to be associated with T2D in Japanese and European descent populations, our results may lead to a better understanding of differences in the molecular pathogenesis of T2D among various populations.
authors.affiliation: School of Post-Baccalaureate Chinese Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
authors.forename: Chi-Fan
authors.initials: CF
authors.lastname: Yang
authors.forename: Ching-Chu
authors.initials: CC
authors.lastname: Chen
authors.forename: Lee-Ming
authors.initials: LM
authors.lastname: Chuang
authors.forename: Chieh-Hsiang
authors.initials: CH
authors.lastname: Lu
authors.forename: Chwen-Tzuei
authors.initials: CT
authors.lastname: Chang
authors.forename: Tzu-Yuan
authors.initials: TY
authors.lastname: Wang
authors.forename: Rong-Hsing
authors.initials: RH
authors.lastname: Chen
authors.forename: Chiung-Fang
authors.initials: CF
authors.lastname: Shiu
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Liu
authors.forename: Chih-Chun
authors.initials: CC
authors.lastname: Chang
authors.forename: Pei
authors.initials: P
authors.lastname: Chen
authors.forename: Chien-Hsiun
authors.initials: CH
authors.lastname: Chen
authors.forename: Cathy S J
authors.initials: CS
authors.lastname: Fann
authors.forename: Yuan-Tsong
authors.initials: YT
authors.lastname: Chen
authors.forename: Jer-Yuarn
authors.initials: JY
authors.lastname: Wu
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015203:Reproducibility of Results
chemical_list: D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human