Cross-ancestry discovery of genetic risk variants for lean metabolic dysfunction-associated steatotic liver disease

This study identified significant associations between genetic variants in PNPLA3 and SAMM50 and lean MASLD in the Taiwan Han Chinese population. The variant rs9625962 exhibited pleiotropic effects, contributing to MASLD regardless of BMI category, triglyceride levels, and liver function profiles. The replication of all significant variants in the All of Us dataset underscores the robustness and generalizability of our findings. These results highlight the importance of genetic factors in lean MASLD pathogenesis and support further investigation into gene-environment interactions.