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

Authors: Takeuchi, F  Serizawa, M  Yamamoto, K  Fujisawa, T  Nakashima, E  Ohnaka, K  Ikegami, H  Sugiyama, T  Katsuya, T  Miyagishi, M  Nakashima, N  Nawata, H  Nakamura, J  Kono, S  Takayanagi, R  Kato, N 
Citation: Takeuchi F, etal., Diabetes. 2009 Jul;58(7):1690-9. Epub 2009 Apr 28.
Pubmed: (View Article at PubMed) PMID:19401414
DOI: Full-text: DOI:10.2337/db08-1494

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.

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RGD Object Information
RGD ID: 2313941
Created: 2009-10-28
Species: All species
Last Modified: 2009-10-28
Status: ACTIVE