title: 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.
abstract: OBJECTIVE
  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.
authors.affiliation: Laboratory for Endocrinology, Metabolism and Kidney Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Department of Internal Medicine, Division of Metabolism and Endocrinology, St. Marianna University School of Medicine, Kawasaki, Japan.
authors.forename: Ren
authors.initials: R
authors.lastname: Matsuba
authors.affiliation: Department of Internal Medicine, Division of Metabolism and Endocrinology, St. Marianna University School of Medicine, Kawasaki, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Sakai
authors.affiliation: Laboratory for Endocrinology, Metabolism and Kidney Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
authors.forename: Minako
authors.initials: M
authors.lastname: Imamura
authors.affiliation: Department of Internal Medicine, Division of Metabolism and Endocrinology, St. Marianna University School of Medicine, Kawasaki, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: First Department of Internal Medicine, University of Toyama, Toyama, Japan; Community Medical Support Unit, Faculty of Medicine, University of Toyama, Toyama, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Iwata
authors.affiliation: Health Center, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hirose
authors.affiliation: Department of Internal Medicine, Kawasaki Medical School, Kurashiki, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Kaku
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maegawa
authors.affiliation: Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan; Sportology Center, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Watada
authors.affiliation: First Department of Internal Medicine, University of Toyama, Toyama, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Tobe
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Atsunori
authors.initials: A
authors.lastname: Kashiwagi
authors.affiliation: Sportology Center, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Kawamori
authors.affiliation: Laboratory for Endocrinology, Metabolism and Kidney Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Department of Advanced Genomic and Laboratory Medicine, Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Maeda
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005060:Europe; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide