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Diabetes. 2009 Jul;58(7):1690-9. doi: 10.2337/db08-1494. Epub 2009 Apr 28.

Confirmation of multiple risk Loci and genetic impacts by a genome-wide association study of type 2 diabetes in the Japanese population.

Author information

1
Department of Medical Ecology and Informatics, Research Institute, International Medical Center of Japan, Tokyo, Japan.

Abstract

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 < 0.0025, stage 1); additionally to direct genotyping, 964 healthy control subjects formed the in silico control panel. Along with genome-wide exploration, we aimed to replicate the disease association of 17 SNPs from 16 candidate loci previously identified in Europeans. The associated and/or replicated loci (23 SNPs; P < 7 x 10(-5) for genome-wide exploration and P < 0.05 for replication) were examined in the stage 3 panel comprising 4,000 case subjects and 12,569 population-based samples, from which 4,889 nondiabetic control subjects were preselected. The 12,569 subjects were used for overall risk assessment in the general population.

RESULTS:

Four loci-1 novel with suggestive evidence (PEPD on 19q13, P = 1.4 x 10(-5)) and three previously reported-were identified; the association of CDKAL1, CDKN2A/CDKN2B, and KCNQ1 were confirmed (P < 10(-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.

PMID:
19401414
PMCID:
PMC2699880
DOI:
10.2337/db08-1494
[Indexed for MEDLINE]
Free PMC Article

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