Joint Effects of Known Type 2 Diabetes Susceptibility Loci in Genome-Wide Association Study of Singapore Chinese: The Singapore Chinese Health Study

Background\ud \ud Genome-wide association studies (GWAS) have identified genetic factors in type 2 diabetes (T2D), mostly among individuals of European ancestry. We tested whether previously identified T2D-associated single nucleotide polymorphisms (SNPs) replicate and whether SNPs in regions near known T2D SNPs were associated with T2D within the Singapore Chinese Health Study.\ud \ud Methods\ud \ud 2338 cases and 2339 T2D controls from the Singapore Chinese Health Study were genotyped for 507,509 SNPs. Imputation extended the genotyped SNPs to 7,514,461 with high estimated certainty (r2>0.8). Replication of known index SNP associations in T2D was attempted. Risk scores were computed as the sum of index risk alleles. SNPs in regions ±100 kb around each index were tested for associations with T2D in conditional fine-mapping analysis.\ud \ud Results\ud \ud Of 69 index SNPs, 20 were genotyped directly and genotypes at 35 others were well imputed. Among the 55 SNPs with data, disease associations were replicated (at p