Hepatogenomics of MAFLD in Asian Population: Genetic Polymorphisms and Pathway-Based Insights

Metabolic dysfunction–associated fatty liver disease (MAFLD) has emerged as a major public health concern across Asia, marked by rising prevalence, younger age at presentation, and variability in clinical course. This variability reflects a complex interplay between metabolic exposures and genetic architecture, contributing to heterogeneity in disease susceptibility and progression. While dietary patterns, sedentary lifestyle, and metabolic comorbidities remain central contributors, inherited susceptibility influences hepatic fat accumulation, progression to steatohepatitis, and fibrotic transformation. This review aims to summarize genetic polymorphisms implicated in MAFLD among Asian populations and to explore their role in identifying individuals at increased inherited risk. A pathway-oriented perspective is adopted to contextualize how these variants contribute to key biological mechanisms underlying MAFLD. A narrative review approach was employed, drawing upon genome-wide association studies, candidate gene analyses, and functional research. Genetic variants were grouped into principal pathogenic pathways, including lipid handling, insulin resistance and de novo lipogenesis, cholesterol metabolism, inflammatory signaling, and fibrogenesis. While emphasis is placed on evidence from Asian cohorts, selected variants are also discussed based on mechanistic relevance, even when direct population-based data remain limited. Differences in allele frequency and effect size between Asian and Western populations were considered to clarify ethnic variation. Among the identified variants, PNPLA3 rs738409 consistently emerges as a dominant determinant of hepatic fat accumulation and adverse histological features. Additional polymorphisms further modulate risk, with some exerting protective effects. Taken together, current evidence supports integrating genetic markers into risk stratification models for earlier recognition of genetically predisposed individuals. This pathway-based synthesis provides a framework for understanding MAFLD heterogeneity in Asian populations and may inform precision-oriented prevention and individualized management.