Recent research has identified 12 genetic variants, including 7 newly discovered ones, that are associated with an increased risk of cirrhosis. These findings emerged from a multi-trait genome-wide association study combining cirrhosis cases and alanine aminotransferase levels across several large cohorts, with validation in additional studies. Among the identified variants were a missense variant in the APOE gene and a noncoding variant near EFN1A. These variants were aggregated into a polygenic score, which revealed that individuals in the highest quintile had a significantly increased risk of cirrhosis (odds ratio 2.26) compared to those in the lowest quintile. The risk was even greater for those in the top 1% of the polygenic score distribution (odds ratio 3.16).

The study also demonstrated that the effects of polygenic risk are amplified by environmental factors such as alcohol consumption and obesity. For individuals with extreme polygenic risk, the probability of developing cirrhosis by age 75 was 13.7%, 20.1%, and 48.2% for those with low, moderate, and high alcohol intake, respectively. Similarly, the risk increased with body mass index, reaching 19.5% for those with obesity. These findings underscore the combined impact of genetic predisposition and lifestyle factors, highlighting the importance of targeted prevention and intervention strategies for individuals at elevated genetic risk.

Reference: Emdin CA, Haas M, Ajmera V, et al. Association of Genetic Variation With Cirrhosis: A Multi-Trait Genome-Wide Association and Gene-Environment Interaction Study. Gastroenterology. 2021 Apr;160(5):1620-1633.e13. doi: 10.1053/j.gastro.2020.12.011. Epub 2020 Dec 11. PMID: 33310085; PMCID: PMC8035329.