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- Title
Confirmation of Multiple Risk Loci and Genetic Impacts by a Genome-Wide Association Study of Type 2 Diabetes in the Japanese Population.
- Authors
Takeuchi, Fumihiko; Serizawa, Masakuni; Yamamoto, Ken; Fujisawa, Tomomi; Nakashima, Eitaro; Ohnaka, Keizo; Ikegami, Hiroshi; Sugiyama, Takao; Katsuya, Tomohiro; Miyagishi, Makoto; Nakashima, Naoki; Nawata, Hajime; Nakamura, Jiro; Kono, Suminori; Takayanagi, Ryoichi; Kato, Norihiro
- Abstract
OBJECTIVE--To identify novel type 2 diabetes gene variants and confirm previously identified ones, a three-staged genomewide 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[sup -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[sup -5]) and three previously reported--were identified; the association of CDKAL1, CDKN2A/CDKN2B, and KCNQ1 were confirmed (P < 10[sup -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 haft of the confirmed type 2 diabetes loci. Diabetes 58: 1690-1699, 2009
- Subjects
HUMAN genetic variation; TYPE 2 diabetes; JAPANESE people; EUROPEANS; GENOMICS; GENETIC polymorphisms; RISK assessment; DISEASE susceptibility; DISEASES
- Publication
Diabetes, 2009, Vol 58, Issue 7, p1690
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db08-1494