TM6SF2 and hepatocellular carcinoma: Moreover, by applying a mendelian randomization approach, Dongiovanni and colleagues firstly reported that the co-presence of PNPLA3, TM6SF2, MBOAT7, and GCKR at-risk alleles, aggregated into a PRS, causally determines an increased susceptibility to develop severe chronic liver diseases, which reached about 13.4-fold for MASLD-HCC risk, as a consequence of their ability to induce hepatic fat accumulation (12).