In multivariable-adjusted Cox proportional hazards regression models that contained each possible combination of the 3 risk factors, we observed synergistic interactions between the PNPLA3 I148M variant, obesity, and excessive alcohol intake that were associated with the risk of incident cirrhosis, HCC, or liver disease–related death (Table 3; Figure 2A). Here, PNPLA3 is linked to hepatocellular carcinoma.