Endocrine Abstracts

Although over 50 type 2 diabetes (T2D) loci have been identified through genome-wide association studies (GWAS), the vast majority of the genetic predisposition to T2D still remains to be clarified. One explanation is that despite the use of high-throughput genotyping arrays, only a small proportion of genetic variants in the human genome are actually surveyed, especially in non-European populations. We explored the comprehensive catalog of genomic variations provided by the 1000 Genomes Project to identify variations conferring susceptibility to T2D in the Japanese population that were not detected in previous scans. We imputed 10,524,368 variants derived from 194 East Asian subjects (June 2011 release) into 5,976 cases and 20,829 controls genotyped by 610K single-nucleotide polymorphism (SNP) array. Overall concordance was good, although imputed SNPs with minor allele frequency (MAF) below 1% apparently contained poorly imputed SNPs. We then tested associations for T2D before and after adjusting for age, sex, and body mass index. We found that in addition to variants of the previously reported loci there were 16 loci harboring multiple variants with a p value lower than 10–5 at 1q32, 5p13, 6p12, 7p12, 7q32, 8p11, 9q31, 9q34, 10p13, 10q23, 11q13, 11q24, 12p11, 15q26, and 17p13. The MAF range was 0.01 to 0.45, and the odds ratios were between 1.10 and 1.48. We are conducting a replication study to confirm the association in another 7,000 cases and 3,500 controls. We also sought to define the most relevant SNPs for susceptibility to T2D in the previously identified genes. We did not find any stronger association with T2D than the originally reported SNPs in our population. However, there is a tendency that lower frequency variants were enriched in those with large effect size. Our study highlights the benefit of using data derived from next-generation sequencing of the human genome such as the 1000 Genomes Project to explore T2D loci more comprehensively.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding

This work was supported, however funding details unavailable.