Associations of Alcohol Consumption and Genetic Predisposition to Hepatic Steatosis With Liver-Related Events: Results From Large Population-Based Cohort Studies

Background & Aims: The new classification for steatotic liver disease identifies 3 phenotypes based on alcohol consumption. The aim of this study was to evaluate the associations between alcohol intake and liver-related events (LREs) across different drinking categories and whether genetic predisposition influences these associations. Methods: Data from 301,673 UK Biobank participants were analyzed. Alcohol consumption was self-reported and categorized by weekly intake as mild (< 140 g for females and < 210 g for males), moderate (140–350 g for females and 210–420 g for males), and heavy (> 350 g in females and > 420 g for males). A polygenic risk score based on 5 well-known single nucleotide polymorphisms associated with hepatic steatosis was calculated. Hazard ratios (HRs) and 95% CIs were calculated using Cox proportional hazard models. The analysis was validated in 47,252 participants from China Kadoorie Biobank. Results: During a median follow-up of 12.8 years, 1742 incident cases of LREs were documented. The multivariable-adjusted HRs per SD increment in alcohol intake for LREs were 0.95 (95% CI, 0.89–1.02) among mild drinkers, 1.23 (95% CI, 1.10–1.37) among moderate drinkers, and 1.18 (95% CI, 1.14–1.22) among heavy drinkers. The associations appeared stronger in those with high genetic risk. Compared with adults with low genetic risk and mild alcohol consumption, those with high genetic risk and heavy alcohol consumption had higher risks of LREs (HR, 6.50; 95% CI, 5.26–8.04; P for interaction < .001). Similar findings were observed in China Kadoorie Biobank. Conclusions: Associations between alcohol intake and LREs vary across different drinking categories. Individuals with a higher genetic risk for steatotic liver disease appear more susceptible to alcohol.