ABSTRACT
Nonalcoholic fatty liver disease (NAFLD) is a leading cause of liver diseases, and its incidence is increasing at an alarming rate. During recent years, evidence has accumulated that NAFLD has a strong heritable component. Genome-wide association studies have uncovered robust and reproducible associations between common variations in genes such as PNPLA3, TM6SF2, MBOAT7, GCKR, HSD17B13 and the full spectrum of liver damage-related NAFLD. These findings have provided compelling new insight into the biology of NAFLD and have highlighted potential attractive pharmaceutical targets. More recently, exome sequencing studies have highlighted also a role of APOB and ATG7 rare variants in NAFLD predisposition. Overall, genetics has revealed that increased intracellular lipid content drives NAFLD development and progression, through a variety of pathways including epigenetic mechanisms. Genetic risk variants can be used to improve disease risk stratification and as a target for novel drugs to enable a precision medicine approach to treat NAFLD.
