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

• Published in: Diabetologia Vol. 52; no. 8; pp. 1554 - 1560
• Main Authors: Omori, S, Tanaka, Y, Horikoshi, M, Takahashi, A, Hara, K, Hirose, H, Kashiwagi, A, Kaku, K, Kawamori, R, Kadowaki, T, Nakamura, Y, Maeda, S
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 01-08-2009; Springer-Verlag; Springer; Springer Nature B.V
• Subjects: Aged; Biological and medical sciences; Cyclin-dependent kinases; Diabetes; Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - genetics; Diabetes. Impaired glucose tolerance; Disease; Disease Susceptibility; Endocrine pancreas. Apud cells (diseases); Endocrinology; Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Genomes; Human Physiology; Humans; Internal Medicine; Japan; Kinases; Male; Medical sciences; Medicine; Medicine & Public Health; Meta-analysis; Meta-Analysis as Topic; Metabolic Diseases; Metabolic disorders; Middle Aged; Minority & ethnic groups; Neoplasm Proteins - genetics; Nuclear weapons; Polymorphism; Polymorphism, Single Nucleotide; Potassium; Risk Assessment; Womens health; Zinc Fingers - genetics; Japan; Type 2 diabetes; Association study; SNP; Japanese; Endocrinopathy; Human; Sensitivity; Association; Risk factor; Metabolic diseases; Replication
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-009-1397-5

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.