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 × 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 × 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.
| Original language | English |
|---|---|
| Pages (from-to) | 1690-1699 |
| Number of pages | 10 |
| Journal | Diabetes |
| Volume | 58 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Jul 1 2009 |
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All Science Journal Classification (ASJC) codes
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
Cite this
Confirmation of multiple risk loci and genetic impacts by a genome-wide association study of type 2 diabetes in the Japanese population. / 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.
In: Diabetes, Vol. 58, No. 7, 01.07.2009, p. 1690-1699.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Confirmation of multiple risk loci and genetic impacts by a genome-wide association study of type 2 diabetes in the Japanese population
AU - Takeuchi, Fumihiko
AU - Serizawa, Masakuni
AU - Yamamoto, Ken
AU - Fujisawa, Tomomi
AU - Nakashima, Eitaro
AU - Ohnaka, Keizo
AU - Ikegami, Hiroshi
AU - Sugiyama, Takao
AU - Katsuya, Tomohiro
AU - Miyagishi, Makoto
AU - Nakashima, Naoki
AU - Nawata, Hajime
AU - Nakamura, Jiro
AU - Kono, Suminori
AU - Takayanagi, Ryoichi
AU - Kato, Norihiro
PY - 2009/7/1
Y1 - 2009/7/1
N2 - 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 × 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 × 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.
AB - 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 × 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 × 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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U2 - 10.2337/db08-1494
DO - 10.2337/db08-1494
M3 - Article
C2 - 19401414
AN - SCOPUS:67650248695
VL - 58
SP - 1690
EP - 1699
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 7
ER -