Confirmation of Multiple Risk Loci and Genetic Impacts by a Genome-Wide Association Study of Type 2 Diabetes in the Japanese Population

OBJECTIVE To identify novel type 2 diabetes gene variants and confirm previously identified ones, a three-staged genome-wide association study was performed in the Japanese population. RESEARCH DESIGN AND METHODS In the stage 1 scan, we genotyped 519 case and 503 control subjects with 482,625 single nucleotide polymorphism (SNP) markers; in the stage 2 panel comprising 1,110 case subjects and 1,014 control subjects, we assessed 1,456 SNPs ( P P –5 for genome-wide exploration and P RESULTS Four loci—1 novel with suggestive evidence ( PEPD on 19q13, P = 1.4 × 10 –5 ) and three previously reported—were identified; the association of CDKAL1 , CDKN2A / CDKN2B, and KCNQ1 were confirmed ( P –19 ). Moreover, significant associations were replicated in five other candidate loci: TCF7L2 , IGF2BP2 , SLC30A8 , HHEX , and KCNJ11 . There was substantial overlap of type 2 diabetes susceptibility genes between the two populations, whereas effect size and explained variance tended to be higher in the Japanese population. CONCLUSIONS The strength of association was more prominent in the Japanese population than in Europeans for more than half of the confirmed type 2 diabetes loci.