PLoS ONE (Jan 2011)

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

DOI
https://doi.org/10.1371/journal.pone.0026911
Journal volume & issue
Vol. 6, no. 10
p. e26911

Abstract

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BackgroundSeveral 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 findingsWe 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 (PConclusionsThese results indicate that IRS1 locus may be common locus for type 2 diabetes across different ethnicities.