A number of studies have identified genetic variants associated with the natural history and severity of NAFLD, NAFLD in lean individuals, risk stratification, and prediction of response to lifestyle or therapeutic intervention; the best characterized and replicated genes emanating from these studies include patatin-like phospholipase domain-containing protein 3 (PNPLA3) and transmembrane 6 superfamily 2 human gene (TM6SF2). This evidence concerns the gene PNPLA3 and metabolic dysfunction-associated steatotic liver disease.