Type 2 diabetes mellitus is a complex polygenic disorder in which common genetics variants interact with environmental factors. Genome-wide association study(GWAS) revealed more than 10 diabetes susceptibility loci for type 2 diabetes mellitus including SNPs in KCNQ1, which was first identified in Japanese by two independent Japanese groups. However, these variants identified by GWAS showed low O.R. (odds ratio) such as 1.1-1.5 suggesting low penetrance of these variants. Diabetes mellitus is also caused by a mutation in one gene such as glucokinase and HNF-1 alpha, which showed high penetrance. Therefore, next challenge will be to identify low-frequency variants with intermediate penetrance, which may be associated with diabetes mellitus.