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

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= Diabetologia

Genetic variants on chromosome 6p21.1 and 6p22.3 are associated with type 2 diabetes risk: a case–control study in Han Chinese

“…A recent replication study with 3388 T2D cases and 2856 controls in a Japanese population failed to repeat the association between rs9472138 and T2D (OR¼1.06, P¼0.41). 35 This finding was inconsistent with our results in Chinese population and might also reflect the difference among different populations. On the other hand, because of the lower allele frequency of rs9472138 that leads to the lower statistical power (about 64%), we could not rule out the possibility of false-positive associations, which needs validation from large studies in the future.…”

Variations in/nearby genes coding for JAZF1, TSPAN8/LGR5 and HHEX-IDE and risk of type 2 diabetes in Han Chinese

“…3 Replication studies in other Asian populations just identified marginal significance of type 2 diabetes risk associated with some of these novel loci. [11][12][13] We thought that the possible reasons for no or marginal significance were the limited sample size of these Asian population studies. To identify the effects of these genes on type 2 diabetes, we conducted a meta-analysis by pooling our data with those reported in the previous studies of East Asians.…”

Reduced body weight in male Tspan8-deficient mice

“…However, no association of this locus with prediabetic traits could be identified in Southern German individuals at an increased risk for T2D; 9 replication of this T2D risk locus could also not be established in a Japanese cohort and an Asian Indian Sikh population containing type 2 diabetics. 10,11 None of the three genes in the T2D risk locus 12q15 (LGR5, PTPRR and TSPAN8) have previously been shown to have a role in the onset or progression of T2D.…”