Genetic basis of Asian diabetes

Area of Science:

• Genomics and Precision Medicine
• Diabetes Research
• Population Genetics

Background:

• Recent genomic studies in Asian populations have significantly improved understanding of diabetes diagnosis, pathophysiology, risk prediction, and precision care.
• Monogenic diabetes (e.g., MODY, mitochondrial diabetes) underscores the need for genetic diagnosis for tailored treatments.
• Genome-wide association studies (GWAS) in East Asian populations reveal unique T2D characteristics, such as earlier onset at lower BMI and increased beta-cell dysfunction.

Purpose of the Study:

• To review recent genomic findings in Asian populations related to various diabetes types.
• To highlight the role of genetic factors in diabetes heterogeneity and incidence variations.
• To discuss the potential and limitations of polygenic risk scores (PRS) in Asian populations and propose strategies for improvement.

Main Methods:

• Review of recent genomic studies, including GWAS and biobank resources, focusing on Asian populations.
• Analysis of genetic contributions to monogenic diabetes, T2D, GDM, and T1D.
• Evaluation of polygenic risk score (PRS) transferability and development of ancestry-aware approaches.

Main Results:

• Genomic studies have identified numerous risk loci for T2D, with distinct features in East Asians.
• Genetic factors, including HLA and non-HLA loci, and potential infectious links, may explain T1D incidence variations in Asia.
• Limited cross-population transferability of PRS in Asian populations necessitates ancestry-matched and trans-ancestry methods.

Conclusions:

• Genomic insights are crucial for advancing diabetes care in Asian populations.
• Improved PRS validation and development of subtype-aware frameworks are needed for equitable precision diabetes care.
• Expanding genomic resources and fostering cross-biobank collaborations across Asia are essential for future progress.