A genome-wide association study identifies susceptibility variants for type 2 diabetes in Han Chinese.
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.
Tsai
Fuu-Jen
FJ
School of Post-Baccalaureate Chinese Medicine, China Medical University, Taichung, Taiwan.
Yang
Chi-Fan
CF
Chen
Ching-Chu
CC
Chuang
Lee-Ming
LM
Lu
Chieh-Hsiang
CH
Chang
Chwen-Tzuei
CT
Wang
Tzu-Yuan
TY
Chen
Rong-Hsing
RH
Shiu
Chiung-Fang
CF
Liu
Yi-Min
YM
Chang
Chih-Chun
CC
Chen
Pei
P
Chen
Chien-Hsiun
CH
Fann
Cathy S J
CS
Chen
Yuan-Tsong
YT
Wu
Jer-Yuarn
JY
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
D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human