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

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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 Nov 2

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ASJC Scopus subject areas

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

Cite this

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, 6(10), [e26911]. https://doi.org/10.1371/journal.pone.0026911