Genetic Risk Amplifies Liver Damage from Alcohol, Long-Term Study Finds
China: A recent study published in the journal Gastroenterology has highlighted how alcohol consumption and genetic predisposition can jointly influence the risk of liver-related complications. Conducted by Dr. Yuanjie Pang and colleagues from the School of Public Health at Peking University, the large-scale analysis provides important insights into the interaction between lifestyle and inherited risk in the development of liver conditions.
Drawing on data from over 300,000 participants in the UK Biobank, the researchers examined how varying levels of alcohol intake impacted the likelihood of liver-related events (LREs) and whether genetic susceptibility to hepatic steatosis—a condition marked by fat accumulation in the liver—altered this relationship. To classify alcohol consumption, participants were grouped into three categories: mild, moderate, and heavy drinkers, based on self-reported weekly intake.
The study led to the following findings:
- Over a median follow-up period of 12.8 years, 1,742 liver-related events were documented.
- Mild alcohol consumption was not significantly linked to an increased risk of liver complications.
- Moderate alcohol intake was associated with a 23% higher risk of liver-related issues compared to mild drinking.
- Heavy drinking was linked to an 18% increased risk of liver complications relative to mild consumption.
- A polygenic risk score based on five genetic markers related to liver fat accumulation was used to assess genetic susceptibility.
- Individuals with high genetic risk who also consumed alcohol heavily had a substantially elevated risk of liver complications.
- Compared to those with low genetic risk and mild alcohol use, individuals with high genetic risk and heavy drinking had a more than sixfold higher risk, with a hazard ratio of 6.50.
To strengthen their findings, the team validated their results using data from an additional 47,252 participants in the China Kadoorie Biobank. Similar patterns were observed, lending cross-population support to the conclusions.
The findings emphasize the importance of considering genetic and behavioral factors when assessing liver disease risk. "Our results indicate that individuals with a genetic predisposition to steatotic liver disease are particularly vulnerable to the harmful effects of alcohol," the authors noted. They emphasized the need for personalized public health strategies, especially for high-risk individuals.
However, the study is not without limitations. The reliance on self-reported alcohol consumption may introduce some degree of reporting bias. Additionally, as an observational study, it cannot definitively establish cause-and-effect relationships.
Still, the research provides a compelling case for more targeted interventions aimed at reducing alcohol-related liver damage, particularly among those genetically predisposed to hepatic steatosis. Further studies are needed to understand better the biological mechanisms underlying the gene-alcohol interaction in liver disease development.
Reference:
Xue, H., Wang, L., Sun, D., Wu, Y., Yu, C., Huang, Y., Chan, S. O., Ling, W., Lv, J., Li, L., Chen, X., Pang, Y., & Yu, C. (2025). Associations of alcohol consumption and genetic predisposition to hepatic steatosis with liver-related events: Results from large population-based cohort studies. Gastroenterology. https://doi.org/10.1053/j.gastro.2025.04.021
