Perspectives on genetic studies of type  2 diabetes from the genome‐wide association studies era to precision medicine

This review summarizes recent advances in the genetics of type  2 diabetes, and discusses the perspective of future investigations for understanding the genetic architecture of type 2 diabetes and its clinical applications. AbstractGenome-wide association studies (GWAS) have facilitated a substantial and rapid increase in the number of confirmed genetic susceptibility variants for complex diseases. Approximately 700 variants predisposing individuals to the risk for type  2 diabetes have been identified through GWAS until 2023. From 2018 to 2022, hundreds of type 2 diabetes susceptibility loci with smaller effect sizes were identified through large-scale GWAS with sample sizes of 200,000 to>1  million. The clinical translation of genetic information for type 2 diabetes includes the development of novel therapeutics and risk predictions. Although drug discovery based on loci identified in GWAS remains challenging owing to the difficulty of functional annotation, global efforts have be en made to identify novel biological mechanisms and therapeutic targets by applying multi-omics approaches or searching for disease-associated coding variants in isolated founder populations. Polygenic risk scores (PRSs), comprising up to millions of associated variants, can identify individuals wit h higher disease risk than those in the general population. In populations of European descent, PRSs constructed from base GWAS data with a sample size of approximately 450,000 have pred...
Source: Journal of Diabetes Investigation - Category: Endocrinology Authors: Tags: REVIEW Source Type: research