Replication of Genome-Wide Association Studies of Type 2 Diabetes Susceptibility in Japan

Background: In Europeans and populations of European origin, several groups have recently identified novel type 2 diabetes susceptibility genes, including FTO, SLC30A8, HHEX, CDKAL1, CDKN2B, and IGF2BP2, none of which were in the list of functional candidates. Objective and Design: The aim of this study was to replicate in a Japanese population previously identified associations of single nucleotide polymorphisms (SNPs) within 10 candidate loci with type 2 diabetes using a relatively large sample size: 1921 subjects with type 2 diabetes and 1622 normal controls. Results: A total of 15 SNPs were genotyped. Eight SNPs in five loci were found to be associated with type 2 diabetes: rs3802177 [odds ratio (OR) = 1.16 (95% confidence interval (CI) 1.05–1.27); P = 4.5 × 10−3] in SLC30A8; rs1111875 [OR = 1.27 (95% CI 1.14–1.40); P = 1.4 × 10−5] and rs7923837 [OR = 1.27 (95% CI 1.13–1.43); P = 1.0 × 10−4] in HHEX; rs10811661 [OR = 1.27 (95% CI 1.15–1.40); P = 1.9 × 10−6] in CDKN2B; rs4402960 [OR = 1.23 (95% CI 1.11–1.36); P = 8.1 × 10−5] and rs1470579 [OR = 1.18 (95% CI 1.07–1.31); P = 8.3 × 10−4] in IGF2BP2; and rs7754840 [OR = 1.28 (95% CI 1.17–1.41); P = 4.5 × 10−7] and rs7756992 [OR = 1.27 (95% CI 1.15–1.40); P = 9.8 × 10−7] in CDKAL1. The first and second strongest associations were found at variants in CDKAL1 and CDKN2B, both of which are involved in the regenerative capacity of pancreatic β-cells. Conclusion: Some of these variants represent common type 2 diabetes-susceptibility genes in both Japanese and Europeans.