GWAS在2型糖尿病相关基因研究中的应用

2型糖尿病(type 2 diabetes,T2D)是一种常见的复杂疾病,其发病受到遗传和环境因素的共同作用.全基因组关联研究(genome-wide association study,GWAS)是一种可在全基因组范围筛查疾病相关的序列变异的新型群体关联研究方法.近年来,采用GWAS以及在此基础上展开的meta分析,已分别在TCF7L2、HHEX-IDE、SLC30A8、CDKAL1、CDKN2A-CDKN2B、IGF2BP2、NOTCH2、CDC123-CAMK1D、ADAMTS9、THADA、TSPAN8-LGR5、JAZF1等12个基因区域鉴定出多个T2D相关的多态位点.已有的研究提示,上述多个基因可能在胰岛β细胞发育和功能维持方面扮演着重要角色.本文集中介绍了GWAS的原理及其在T2D研究中的优势;回顾了GWAS在T2D研究中的主要发现;并对运用GWAS在T2D研究中尚需解决的问题进行了总结和展望.

Application of GWAS in the Type 2 Diabetes Associated Gene Study

Type 2 diabetes（T2D）is a common complex disease, resulting from the interaction between genetic and environmental factors. As a new type of population-based association study，genome-wide association study（GWAS）can be used to detect sequence variations related to diseases in the range of whole genome. During the past years, through GWAS approach and further studies of mata-analysis, many polymorphic sites have been confirmed in 12 gene regions, including TCF7L2, HHEX-IDE, SLC30A8, CDKAL1,CDKN2A-CDKN2B,IGF2BP2,NOTCH2,CDC123-CAMK1D,ADAMTS9,THADA,TSPAN8/LGR5, JAZF1.The existing studies suggested that many of these genes may play important roles in pancreatic beta-cell development and function. In the present paper, some comments on GWAS were reviewed，including the principle of GWAS, advantages of GWAS in the studies of T2D, and primary findings of GWAS on T2D. This paper also summarized the shortcomings of current GWAS on T2D and perspectives of its future.