Genetic markers of type 2 diabetes: Progress in genome‐wide association studies and clinical application for risk prediction

Type 2 diabetes (T2D) has become a leading public health challenge worldwide. To date, a total of 83 susceptibility loci for T2D have been identified by genome-wide association studies (GWAS). Application of meta-analysis and modern genotype imputation approaches to GWAS data from diverse ethnic populations has been key in the effort to discover T2D loci. Genetic information is expected to play a vital role in the prediction of T2D, and many efforts have been made to develop T2D risk models that include both conventional and genetic risk factors. Yet, because most T2D genetic variants identified have small effect size individually (10%–20% increased risk of T2D per risk allele), their clinical utility remains unclear. Most studies report that a genetic risk score combining multiple T2D genetic variants does not substantially improve T2D risk prediction beyond conventional risk factors. In this article, we summarize the recent progress of T2D GWAS and further review the incremental predictive performance of genetic markers for T2D. 摘要 2型糖尿病已经成为全球公共卫生的主要挑战。迄今为止,通过全基因组关联研究(genome-wide association studies,GWAS)总共已经鉴定出了83个2型糖尿病易感位点。为了发现2型糖尿病位点,目前主要是致力于应用meta分析以及使用现代基因型归责法来分析从不同种族人群中获得的GWAS数据。期望遗传信息能够在2型糖尿病的预测中发挥其重要作用,并且目前已经在努力研制包括常规与遗传危险因素在内的2型糖尿病风险模型。然而,因为大部分已经鉴定出来的2型糖尿病遗传变异各自都只有很小程度的效应(每个风险等位基因可导致风险增加10%-20%),它们的临床实用价值尚未明确。对于改善2型糖尿病风险预测性能来说,大部分研究所报告的结合了多个2型糖尿病遗传变异的风险预测评分实际上并没有超越常规的危险因素。在这篇文章中,我们概述了2型糖尿病GWAS的最新进展并对2型糖尿病遗传标志所增加的预测性能作出了进一步的综述。