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Replication Study in a Japanese Population to Evaluate the Association between 10 SNP Loci, Identified in European Genome-Wide Association Studies, and Type 2 Diabetes

Author

Listed:
  • Ren Matsuba
  • Kensuke Sakai
  • Minako Imamura
  • Yasushi Tanaka
  • Minoru Iwata
  • Hiroshi Hirose
  • Kohei Kaku
  • Hiroshi Maegawa
  • Hirotaka Watada
  • Kazuyuki Tobe
  • Atsunori Kashiwagi
  • Ryuzo Kawamori
  • Shiro Maeda

Abstract

Aim: We performed a replication study in a Japanese population to evaluate the association between type 2 diabetes and 7 susceptibility loci originally identified by European genome-wide association study (GWAS) in 2012: ZMIZ1, KLHDC5, TLE1, ANKRD55, CILP2, MC4R, and BCAR1. We also examined the association of 3 additional loci: CCND2 and GIPR, identified in sex-differentiated analyses, and LAMA1, which was shown to be associated with non-obese European type 2 diabetes. Methods: We genotyped 6,972 Japanese participants (4,280 type 2 diabetes patients and 2,692 controls) for each of the 10 single nucleotide polymorphisms (SNPs): rs12571751 in ZMIZ1, rs10842994 near KLHDC5, rs2796441 near TLE1, rs459193 near ANKRD55, rs10401969 in CILP2, rs12970134 near MC4R, rs7202877 near BCAR1, rs11063069 near CCND2, rs8108269 near GIPR, and rs8090011 in LAMA1 using a multiplex polymerase chain reaction invader assay. The association of each SNP locus with the disease was evaluated using a logistic regression analysis. Results: All SNPs examined in this study had the same direction of effect (odds ratio > 1.0, p = 9.77 × 10-4, binomial test), as in the original reports. Among them, rs12571751 in ZMIZ1 was significantly associated with type 2 diabetes [p = 0.0041, odds ratio = 1.123, 95% confidence interval 1.037–1.215, adjusted for sex, age and body mass index (BMI)], but we did not observe significant association of the remaining 9 SNP loci with type 2 diabetes in the present Japanese population (p ≥ 0.005). A genetic risk score, constructed from the sum of risk alleles for the 7 SNP loci identified by un-stratified analyses in the European GWAS meta-analysis were associated with type 2 diabetes in the present Japanese population (p = 2.3 × 10-4, adjusted for sex, age and BMI). Conclusions: ZMIZ1 locus has a significant effect on conferring susceptibility to type 2 diabetes also in the Japanese population.

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  • Ren Matsuba & Kensuke Sakai & Minako Imamura & Yasushi Tanaka & Minoru Iwata & Hiroshi Hirose & Kohei Kaku & Hiroshi Maegawa & Hirotaka Watada & Kazuyuki Tobe & Atsunori Kashiwagi & Ryuzo Kawamori & S, 2015. "Replication Study in a Japanese Population to Evaluate the Association between 10 SNP Loci, Identified in European Genome-Wide Association Studies, and Type 2 Diabetes," PLOS ONE, Public Library of Science, vol. 10(5), pages 1-13, May.
    • Handle: RePEc:plo:pone00:0126363
    DOI: 10.1371/journal.pone.0126363
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    1. Kensuke Sakai & Minako Imamura & Yasushi Tanaka & Minoru Iwata & Hiroshi Hirose & Kohei Kaku & Hiroshi Maegawa & Hirotaka Watada & Kazuyuki Tobe & Atsunori Kashiwagi & Ryuzo Kawamori & Shiro Maeda, 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, Public Library of Science, vol. 8(9), pages 1-1, September.
    2. John R B Perry & Benjamin F Voight & Loïc Yengo & Najaf Amin & Josée Dupuis & Martha Ganser & Harald Grallert & Pau Navarro & Man Li & Lu Qi & Valgerdur Steinthorsdottir & Robert A Scott & Peter Almgr, 2012. "Stratifying Type 2 Diabetes Cases by BMI Identifies Genetic Risk Variants in LAMA1 and Enrichment for Risk Variants in Lean Compared to Obese Cases," PLOS Genetics, Public Library of Science, vol. 8(5), pages 1-14, May.
    3. Robert Sladek & Ghislain Rocheleau & Johan Rung & Christian Dina & Lishuang Shen & David Serre & Philippe Boutin & Daniel Vincent & Alexandre Belisle & Samy Hadjadj & Beverley Balkau & Barbara Heude &, 2007. "A genome-wide association study identifies novel risk loci for type 2 diabetes," Nature, Nature, vol. 445(7130), pages 881-885, February.
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