We have firstly exploited a mendelian randomization analysis and a PRS to prove that fatty liver is the main driver of advanced liver damage and that the effect of PNPLA3, TM6SF2, MBOAT7 and GCKR at-risk alleles on hepatic injuries is directly proportional to their ability to promote hepatic fat deposition [33]. Here, PNPLA3 is linked to fatty liver disease.