Replication Study for the Association of 9 East Asian GWAS-Derived Loci with Susceptibility to Type 2 Diabetes in a Japanese Population

Kensuke Sakai, Minako Imamura, Yasushi Tanaka, Minoru Iwata, Hiroshi Hirose, Kohei Kaku, Hiroshi Maegawa, Hirotaka Watada, Kazuyuki Tobe, Atsunori Kashiwagi, Ryuzo Kawamori, Shiro Maeda

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Abstract

Aims:East Asian genome-wide association studies (GWAS) for type 2 diabetes identified 8 loci with genome-wide significance, and 2 loci with a borderline association. However, the associations of these loci except MAEA locus with type 2 diabetes have not been evaluated in independent East Asian cohorts. We performed a replication study to investigate the association of these susceptibility loci with type 2 diabetes in an independent Japanese population.Methods:We genotyped 7,379 Japanese participants (5,315 type 2 diabetes and 2,064 controls) for each of the 9 single nucleotide polymorphisms (SNPs), rs7041847 in GLIS3, rs6017317 in FITM2-R3HDML-HNF4A, rs6467136 near GCCI-PAX4, rs831571 near PSMD6, rs9470794 in ZFAND3, rs3786897 in PEPD, rs1535500 in KCNK16, rs16955379 in CMIP, and rs17797882 near WWOX. Because the sample size in this study was not sufficient to replicate single SNP associations, we constructed a genetic risk score (GRS) by summing a number of risk alleles of the 9 SNPs, and examined the association of the GRS with type 2 diabetes using logistic regression analysis.Results:With the exception of rs1535500 in KCNK16, all SNPs had the same direction of effect (odds ratio [OR]>1.0) as in the original reports. The GRS constructed from the 9 SNPs was significantly associated with type 2 diabetes in the Japanese population (p = 4.0 × 10-4, OR = 1.05, 95% confidence interval: 1.02-1.09). In quantitative trait analyses, rs16955379 in CMIP was nominally associated with a decreased homeostasis model assessment of β-cell function and with increased fasting plasma glucose, but neither the individual SNPs nor the GRS showed a significant association with the glycemic traits.Conclusions:These results indicate that 9 loci that were identified in the East Asian GWAS meta-analysis have a significant effect on the susceptibility to type 2 diabetes in the Japanese population.

Original languageEnglish
Article numbere76317
JournalPLoS One
Volume8
Issue number9
DOIs
Publication statusPublished - 2013 Sep 25

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Genome-Wide Association Study
Medical problems
noninsulin-dependent diabetes mellitus
Type 2 Diabetes Mellitus
Polymorphism
single nucleotide polymorphism
Genes
Single Nucleotide Polymorphism
Nucleotides
loci
Population
odds ratio
Odds Ratio
genome-wide association study
quantitative traits
meta-analysis
Regression analysis
Sample Size
fasting
Meta-Analysis

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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Replication Study for the Association of 9 East Asian GWAS-Derived Loci with Susceptibility to Type 2 Diabetes in a Japanese Population. / Sakai, Kensuke; Imamura, Minako; Tanaka, Yasushi; Iwata, Minoru; Hirose, Hiroshi; Kaku, Kohei; Maegawa, Hiroshi; Watada, Hirotaka; Tobe, Kazuyuki; Kashiwagi, Atsunori; Kawamori, Ryuzo; Maeda, Shiro.

In: PLoS One, Vol. 8, No. 9, e76317, 25.09.2013.

Research output: Contribution to journalArticle

Sakai, K, Imamura, M, Tanaka, Y, Iwata, M, Hirose, H, Kaku, K, Maegawa, H, Watada, H, Tobe, K, Kashiwagi, A, Kawamori, R & Maeda, S 2013, 'Replication Study for the Association of 9 East Asian GWAS-Derived Loci with Susceptibility to Type 2 Diabetes in a Japanese Population', PLoS One, vol. 8, no. 9, e76317. https://doi.org/10.1371/journal.pone.0076317
Sakai, Kensuke ; Imamura, Minako ; Tanaka, Yasushi ; Iwata, Minoru ; Hirose, Hiroshi ; Kaku, Kohei ; Maegawa, Hiroshi ; Watada, Hirotaka ; Tobe, Kazuyuki ; Kashiwagi, Atsunori ; Kawamori, Ryuzo ; Maeda, Shiro. / Replication Study for the Association of 9 East Asian GWAS-Derived Loci with Susceptibility to Type 2 Diabetes in a Japanese Population. In: PLoS One. 2013 ; Vol. 8, No. 9.
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abstract = "Aims:East Asian genome-wide association studies (GWAS) for type 2 diabetes identified 8 loci with genome-wide significance, and 2 loci with a borderline association. However, the associations of these loci except MAEA locus with type 2 diabetes have not been evaluated in independent East Asian cohorts. We performed a replication study to investigate the association of these susceptibility loci with type 2 diabetes in an independent Japanese population.Methods:We genotyped 7,379 Japanese participants (5,315 type 2 diabetes and 2,064 controls) for each of the 9 single nucleotide polymorphisms (SNPs), rs7041847 in GLIS3, rs6017317 in FITM2-R3HDML-HNF4A, rs6467136 near GCCI-PAX4, rs831571 near PSMD6, rs9470794 in ZFAND3, rs3786897 in PEPD, rs1535500 in KCNK16, rs16955379 in CMIP, and rs17797882 near WWOX. Because the sample size in this study was not sufficient to replicate single SNP associations, we constructed a genetic risk score (GRS) by summing a number of risk alleles of the 9 SNPs, and examined the association of the GRS with type 2 diabetes using logistic regression analysis.Results:With the exception of rs1535500 in KCNK16, all SNPs had the same direction of effect (odds ratio [OR]>1.0) as in the original reports. The GRS constructed from the 9 SNPs was significantly associated with type 2 diabetes in the Japanese population (p = 4.0 × 10-4, OR = 1.05, 95{\%} confidence interval: 1.02-1.09). In quantitative trait analyses, rs16955379 in CMIP was nominally associated with a decreased homeostasis model assessment of β-cell function and with increased fasting plasma glucose, but neither the individual SNPs nor the GRS showed a significant association with the glycemic traits.Conclusions:These results indicate that 9 loci that were identified in the East Asian GWAS meta-analysis have a significant effect on the susceptibility to type 2 diabetes in the Japanese population.",
author = "Kensuke Sakai and Minako Imamura and Yasushi Tanaka and Minoru Iwata and Hiroshi Hirose and Kohei Kaku and Hiroshi Maegawa and Hirotaka Watada and Kazuyuki Tobe and Atsunori Kashiwagi and Ryuzo Kawamori and Shiro Maeda",
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AU - Sakai, Kensuke

AU - Imamura, Minako

AU - Tanaka, Yasushi

AU - Iwata, Minoru

AU - Hirose, Hiroshi

AU - Kaku, Kohei

AU - Maegawa, Hiroshi

AU - Watada, Hirotaka

AU - Tobe, Kazuyuki

AU - Kashiwagi, Atsunori

AU - Kawamori, Ryuzo

AU - Maeda, Shiro

PY - 2013/9/25

Y1 - 2013/9/25

N2 - Aims:East Asian genome-wide association studies (GWAS) for type 2 diabetes identified 8 loci with genome-wide significance, and 2 loci with a borderline association. However, the associations of these loci except MAEA locus with type 2 diabetes have not been evaluated in independent East Asian cohorts. We performed a replication study to investigate the association of these susceptibility loci with type 2 diabetes in an independent Japanese population.Methods:We genotyped 7,379 Japanese participants (5,315 type 2 diabetes and 2,064 controls) for each of the 9 single nucleotide polymorphisms (SNPs), rs7041847 in GLIS3, rs6017317 in FITM2-R3HDML-HNF4A, rs6467136 near GCCI-PAX4, rs831571 near PSMD6, rs9470794 in ZFAND3, rs3786897 in PEPD, rs1535500 in KCNK16, rs16955379 in CMIP, and rs17797882 near WWOX. Because the sample size in this study was not sufficient to replicate single SNP associations, we constructed a genetic risk score (GRS) by summing a number of risk alleles of the 9 SNPs, and examined the association of the GRS with type 2 diabetes using logistic regression analysis.Results:With the exception of rs1535500 in KCNK16, all SNPs had the same direction of effect (odds ratio [OR]>1.0) as in the original reports. The GRS constructed from the 9 SNPs was significantly associated with type 2 diabetes in the Japanese population (p = 4.0 × 10-4, OR = 1.05, 95% confidence interval: 1.02-1.09). In quantitative trait analyses, rs16955379 in CMIP was nominally associated with a decreased homeostasis model assessment of β-cell function and with increased fasting plasma glucose, but neither the individual SNPs nor the GRS showed a significant association with the glycemic traits.Conclusions:These results indicate that 9 loci that were identified in the East Asian GWAS meta-analysis have a significant effect on the susceptibility to type 2 diabetes in the Japanese population.

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