Genetic basis of Asian diabetes.

Abstract

Recent genomic studies in Asian populations have advanced our understanding of the diagnosis, pathophysiology, risk prediction, and precision care of diabetes. Monogenic diabetes, including maturity-onset diabetes of the young (MODY) and mitochondrial diabetes, highlights the importance of genetic diagnosis for subtype-specific care. For type 2 diabetes (T2D), genome-wide association studies (GWAS) using large-scale biobank resources have identified numerous risk loci across the genome. These studies have emphasized characteristic features of East Asian T2D, including onset at lower BMI and relatively greater contributions from beta-cell dysfunction pathway. Genetic studies of gestational diabetes mellitus (GDM) have revealed both T2D-related and predominantly gestational components. For type 1 diabetes (T1D), population-specific HLA and non-HLA immune-related loci and possible links to infectious exposures may partly explain global variation in incidence, including lower rates in Asian populations. Polygenic risk scores (PRS) can support risk stratification for diabetes onset and complications, but their implementation in Asian populations is limited by reduced cross-population transferability. Ancestry-matched and trans-ancestry approaches are therefore needed to improve prediction and reduce disparities. Subtype-aware frameworks, including clinical clustering, pathway-specific PRS, and BMI-stratified PRS, may further improve mechanistic interpretation and prediction. Expanding genomic resources across East, Southeast, and South Asia and promoting cross-biobank studies will be essential for improving diabetes genomic research, PRS validation, and equitable precision diabetes care.