Association of new loci identified in European genome-wide association studies with susceptibility to type 2 diabetes in the Japanese

Toshihiko Ohshige, Minoru Iwata, Shintaro Omori, Yasushi Tanaka, Hiroshi Hirose, Kohei Kaku, Hiroshi Maegawa, Hirotaka Watada, Atsunori Kashiwagi, Ryuzo Kawamori, Kazuyuki Tobe, Takashi Kadowaki, Yusuke Nakamura, Shiro Maeda

Research output: Contribution to journalArticle

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Abstract

Background: Several novel susceptibility loci for type 2 diabetes have been identified through genome-wide association studies (GWAS) for type 2 diabetes or quantitative traits related to glucose metabolism in European populations. To investigate the association of the 13 new European GWAS-derived susceptibility loci with type 2 diabetes in the Japanese population, we conducted a replication study using 3 independent Japanese case-control studies. Methodology/Principal Findings: We examined the association of single nucleotide polymorphisms (SNPs) within 13 loci (MTNR1B, GCK, IRS1, PROX1, BCL11A, ZBED3, KLF14, TP53INP1, KCNQ1, CENTD2, HMGA2, ZFAND6 and PRC1) with type 2 diabetes using 4,964 participants (2,839 cases and 2,125 controls) from 3 independent Japanese samples. The association of each SNP with type 2 diabetes was analyzed by logistic regression analysis. Further, we performed combined meta-analyses for the 3 studies and previously performed Japanese GWAS data (4,470 cases vs. 3,071 controls). The meta-analysis revealed that rs2943641 in the IRS1 locus was significantly associated with type 2 diabetes, (P = 0.0034, OR = 1.15 95% confidence interval; 1.05-1.26) and 3 SNPs, rs10930963 in the MTNR1B locus, rs972283 in the KLF14 locus, and rs231362 in the KCNQ1 locus, had nominal association with type 2 diabetes in the present Japanese samples (P<0.05). Conclusions: These results indicate that IRS1 locus may be common locus for type 2 diabetes across different ethnicities.

Original languageEnglish
Article numbere26911
JournalPLoS One
Volume6
Issue number10
DOIs
Publication statusPublished - 2011

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Genome-Wide Association Study
Medical problems
noninsulin-dependent diabetes mellitus
Type 2 Diabetes Mellitus
Genes
loci
Polymorphism
Single Nucleotide Polymorphism
single nucleotide polymorphism
Nucleotides
Meta-Analysis
genome-wide association study
Metabolism
Regression analysis
Population
nationalities and ethnic groups
case-control studies
quantitative traits
Logistics
Case-Control Studies

ASJC Scopus subject areas

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

Cite this

Association of new loci identified in European genome-wide association studies with susceptibility to type 2 diabetes in the Japanese. / Ohshige, Toshihiko; Iwata, Minoru; Omori, Shintaro; Tanaka, Yasushi; Hirose, Hiroshi; Kaku, Kohei; Maegawa, Hiroshi; Watada, Hirotaka; Kashiwagi, Atsunori; Kawamori, Ryuzo; Tobe, Kazuyuki; Kadowaki, Takashi; Nakamura, Yusuke; Maeda, Shiro.

In: PLoS One, Vol. 6, No. 10, e26911, 2011.

Research output: Contribution to journalArticle

Ohshige, T, Iwata, M, Omori, S, Tanaka, Y, Hirose, H, Kaku, K, Maegawa, H, Watada, H, Kashiwagi, A, Kawamori, R, Tobe, K, Kadowaki, T, Nakamura, Y & Maeda, S 2011, 'Association of new loci identified in European genome-wide association studies with susceptibility to type 2 diabetes in the Japanese', PLoS One, vol. 6, no. 10, e26911. https://doi.org/10.1371/journal.pone.0026911
Ohshige, Toshihiko ; Iwata, Minoru ; Omori, Shintaro ; Tanaka, Yasushi ; Hirose, Hiroshi ; Kaku, Kohei ; Maegawa, Hiroshi ; Watada, Hirotaka ; Kashiwagi, Atsunori ; Kawamori, Ryuzo ; Tobe, Kazuyuki ; Kadowaki, Takashi ; Nakamura, Yusuke ; Maeda, Shiro. / Association of new loci identified in European genome-wide association studies with susceptibility to type 2 diabetes in the Japanese. In: PLoS One. 2011 ; Vol. 6, No. 10.
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abstract = "Background: Several novel susceptibility loci for type 2 diabetes have been identified through genome-wide association studies (GWAS) for type 2 diabetes or quantitative traits related to glucose metabolism in European populations. To investigate the association of the 13 new European GWAS-derived susceptibility loci with type 2 diabetes in the Japanese population, we conducted a replication study using 3 independent Japanese case-control studies. Methodology/Principal Findings: We examined the association of single nucleotide polymorphisms (SNPs) within 13 loci (MTNR1B, GCK, IRS1, PROX1, BCL11A, ZBED3, KLF14, TP53INP1, KCNQ1, CENTD2, HMGA2, ZFAND6 and PRC1) with type 2 diabetes using 4,964 participants (2,839 cases and 2,125 controls) from 3 independent Japanese samples. The association of each SNP with type 2 diabetes was analyzed by logistic regression analysis. Further, we performed combined meta-analyses for the 3 studies and previously performed Japanese GWAS data (4,470 cases vs. 3,071 controls). The meta-analysis revealed that rs2943641 in the IRS1 locus was significantly associated with type 2 diabetes, (P = 0.0034, OR = 1.15 95{\%} confidence interval; 1.05-1.26) and 3 SNPs, rs10930963 in the MTNR1B locus, rs972283 in the KLF14 locus, and rs231362 in the KCNQ1 locus, had nominal association with type 2 diabetes in the present Japanese samples (P<0.05). Conclusions: These results indicate that IRS1 locus may be common locus for type 2 diabetes across different ethnicities.",
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T1 - Association of new loci identified in European genome-wide association studies with susceptibility to type 2 diabetes in the Japanese

AU - Ohshige, Toshihiko

AU - Iwata, Minoru

AU - Omori, Shintaro

AU - Tanaka, Yasushi

AU - Hirose, Hiroshi

AU - Kaku, Kohei

AU - Maegawa, Hiroshi

AU - Watada, Hirotaka

AU - Kashiwagi, Atsunori

AU - Kawamori, Ryuzo

AU - Tobe, Kazuyuki

AU - Kadowaki, Takashi

AU - Nakamura, Yusuke

AU - Maeda, Shiro

PY - 2011

Y1 - 2011

N2 - Background: Several novel susceptibility loci for type 2 diabetes have been identified through genome-wide association studies (GWAS) for type 2 diabetes or quantitative traits related to glucose metabolism in European populations. To investigate the association of the 13 new European GWAS-derived susceptibility loci with type 2 diabetes in the Japanese population, we conducted a replication study using 3 independent Japanese case-control studies. Methodology/Principal Findings: We examined the association of single nucleotide polymorphisms (SNPs) within 13 loci (MTNR1B, GCK, IRS1, PROX1, BCL11A, ZBED3, KLF14, TP53INP1, KCNQ1, CENTD2, HMGA2, ZFAND6 and PRC1) with type 2 diabetes using 4,964 participants (2,839 cases and 2,125 controls) from 3 independent Japanese samples. The association of each SNP with type 2 diabetes was analyzed by logistic regression analysis. Further, we performed combined meta-analyses for the 3 studies and previously performed Japanese GWAS data (4,470 cases vs. 3,071 controls). The meta-analysis revealed that rs2943641 in the IRS1 locus was significantly associated with type 2 diabetes, (P = 0.0034, OR = 1.15 95% confidence interval; 1.05-1.26) and 3 SNPs, rs10930963 in the MTNR1B locus, rs972283 in the KLF14 locus, and rs231362 in the KCNQ1 locus, had nominal association with type 2 diabetes in the present Japanese samples (P<0.05). Conclusions: These results indicate that IRS1 locus may be common locus for type 2 diabetes across different ethnicities.

AB - Background: Several novel susceptibility loci for type 2 diabetes have been identified through genome-wide association studies (GWAS) for type 2 diabetes or quantitative traits related to glucose metabolism in European populations. To investigate the association of the 13 new European GWAS-derived susceptibility loci with type 2 diabetes in the Japanese population, we conducted a replication study using 3 independent Japanese case-control studies. Methodology/Principal Findings: We examined the association of single nucleotide polymorphisms (SNPs) within 13 loci (MTNR1B, GCK, IRS1, PROX1, BCL11A, ZBED3, KLF14, TP53INP1, KCNQ1, CENTD2, HMGA2, ZFAND6 and PRC1) with type 2 diabetes using 4,964 participants (2,839 cases and 2,125 controls) from 3 independent Japanese samples. The association of each SNP with type 2 diabetes was analyzed by logistic regression analysis. Further, we performed combined meta-analyses for the 3 studies and previously performed Japanese GWAS data (4,470 cases vs. 3,071 controls). The meta-analysis revealed that rs2943641 in the IRS1 locus was significantly associated with type 2 diabetes, (P = 0.0034, OR = 1.15 95% confidence interval; 1.05-1.26) and 3 SNPs, rs10930963 in the MTNR1B locus, rs972283 in the KLF14 locus, and rs231362 in the KCNQ1 locus, had nominal association with type 2 diabetes in the present Japanese samples (P<0.05). Conclusions: These results indicate that IRS1 locus may be common locus for type 2 diabetes across different ethnicities.

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