PNPLA3 and fatty liver disease: In more detail, Dongiovanni and colleagues used a mendelian randomization analysis and a polygenic risk score (PRS), and established that fatty liver is the main driver of advanced NAFLD up to HCC and the impact of risk alleles in PNPLA3 C > G, TM6SF2 C > T, MBOAT7 C > T, and GCKR C > T on liver damage is directly proportional to their effect size on hepatic fat accumulation [103].