报告题目：Genetic study of type 2 diabetes in Japan
报 告 人: Prof. Shiro Maeda
Department of Advanced Genomic and Laboratory Medicine, Graduate School of Medicine, University of the Ryukyus
Division of Clinical Laboratory and Blood Transfusion, University of the Ryukyus Hospital
Laboratory for Endocrinology, Metabolism and Kidney diseases, RIKEN Center for Integrative Medical Sciences
摘要：After the completion of human genome project, development of single nucleotide polymorphism (SNP) typing technology and collation of information regarding linkage disequilibrium in the human genome have facilitated genome-wide association studies (GWAS) for investigating genes associated with disease susceptibility across the entire human genome. During recent decade, GWAS have provided many genomic information regarding susceptibility to several common diseases, and responsiveness and/or adverse effects to certain drugs. In 2008, we identified KCNQ1 as a novel susceptibility locus for type 2 diabetes through Japanese GWAS (Unoki et al., Nat Genet, 2008). Subsequently, we expanded our GWAS by increasing both sample size and number of examined SNPs, and identified new loci for type 2 diabetes, UBE2E2, C2CD4A-C2CD4B (Yamauchi et al. Nat Genet, 2010), ANK1 locus (Imamura et al. Hum Mol Genet, 2012), MIR129-LEP, GPSM1, SLC16A11-SLC16A13 (Hara et al. Hum Mol Genet, 2014). Recently, we conducted a meta-analysis of GWAS for type 2 diabetes in the Japanese population. Combined data from discovery and subsequent validation analyses (23,399 type 2 diabetes cases and 31,722 controls) have identified 7 new loci for Japanese type 2 diabetes, CCDC85A, FAM60A, DMRTA1, ASB3, ATP8B2, MIR4686 and INAFM2 (Imamura et al. Nat Commun, 2016). Until now, approximately 100 genetic loci have been identified and confirmed as susceptibility to type 2 diabetes through GWAS in different ethnic groups, including Japanese, European, East Asian and South Asian populations. However, integration of these information accounts for less than 20 % of the disease heritability, and thus most of the heritability of type 2 diabetes remain to be identified. Since the rationale of GWAS is based on the hypothesis that common variants contribute to the susceptibility to common diseases, common disease-common variant hypothesis, GWAS have selectively identified common susceptibility variants (allele frequency ≥ 0.05) with lower effect size (odds ratio < 1.5), that is a limitation of the GWAS approach. Although GWAS have brought a significant breakthrough in the field of genetic study for life-style related diseases, new approaches other than GWAS, such as whole genome sequencing to identify rare variants with a greater effect size or integration of genetic and environmental information, will be required to elucidate a heritability of type 2 diabetes completely.