Replication study for the association of new meta-analysis-derived risk loci with susceptibility to type 2 diabetes in 6,244 Japanese individuals

Diabetologia. 2009 Aug;52(8):1554-60. doi: 10.1007/s00125-009-1397-5. Epub 2009 May 20.

Abstract

Aims/hypothesis: Additional susceptibility loci for type 2 diabetes have been identified by a meta-analysis of genome-wide association studies (GWASs) in European populations. To examine further the roles of these new loci, we performed a replication study for the association of these single-nucleotide polymorphism (SNP) loci with the disease in three independent Japanese populations.

Methods: We genotyped seven of the 11 SNPs that emerged in stage 2 of the meta-analysis for European GWASs (rs864745 in JAZF1, rs12779790 near CDC123/CAMK1D, rs7961581 near TSPAN8/LGR5, rs4607103 near ADAMTS9, rs10923931 in NOTCH2, rs1153188 near DCD and rs9472138 near VEGFA) for three independent Japanese populations (first set, 1,630 type 2 diabetes patients vs 1,064 controls; second set, 1,272 type 2 diabetes patients vs 856 controls; third set, 486 type 2 diabetes patients vs 936 controls) using a TaqMan assay. The association of the SNP loci in each population was analysed using a logistic regression analysis, adjusting for age, sex and BMI, and the data were evaluated by a meta-analysis.

Results: A meta-analysis for the three case-control studies identified a nominal association of rs864745 in JAZF1 with type 2 diabetes (OR 1.148, 95% CI 1.034-1.275, p = 0.0098, corrected p = 0.069). The association of other loci did not reach statistically significant levels (nominal p > 0.05).

Conclusions/interpretation: From these results the contribution of these seven loci in conferring susceptibility to type 2 diabetes is considered minor in the Japanese population, if they are present.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Co-Repressor Proteins
  • DNA-Binding Proteins
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Diabetes Mellitus, Type 2 / genetics*
  • Disease Susceptibility
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study*
  • Humans
  • Japan
  • Male
  • Meta-Analysis as Topic
  • Middle Aged
  • Neoplasm Proteins / genetics
  • Polymorphism, Single Nucleotide*
  • Risk Assessment
  • Zinc Fingers / genetics

Substances

  • Co-Repressor Proteins
  • DNA-Binding Proteins
  • JAZF1 protein, human
  • Neoplasm Proteins