A GWAS of non-synonymous single nucleotide polymorphisms (SNPs) in NAFLD identified the rs738409 variant (C.444 C>G p.Ile148Met) in the PNPLA3 gene as the major genetic determinant of inter-individual and ethnicity-related differences in hepatic fat content and the major predictor of predisposition to progressive liver damage, influencing also the response to therapeutic approaches [54]. This evidence concerns the gene PNPLA3 and metabolic dysfunction-associated steatotic liver disease.