Binge-pattern alcohol consumption and genetic risk as determinants of alcohol-related liver disease

• Published in: Nature communications 2023-12, Vol.14 (1), p.8041-8, Article 8041
• Main Authors: Ding, Chengyi, Ng Fat, Linda, Britton, Annie, Im, Pek Kei, Lin, Kuang, Topiwala, Anya, Li, Liming, Chen, Zhengming, Millwood, Iona Y., Bell, Steven, Mehta, Gautam
• Format: Article
• Language: English
• Subjects: 45/43; 631/208/205/2138; 692/308/174; 692/4020/4021/1607/1608; Adult; Alcohol; Alcohol Drinking - adverse effects; Alcohol Drinking - genetics; Alcohol use; Alcoholic beverages; Alcohols; Binge drinking; Binge Drinking - epidemiology; Binge Drinking - genetics; Cirrhosis; COVID-19; Diabetes; Diabetes Mellitus; Drinking behavior; Ethanol; Genetic factors; Genetic Predisposition to Disease; Genetics; Health promotion; Health risk assessment; Humanities and Social Sciences; Humans; Liver; Liver Diseases; multidisciplinary; Pandemics; Public health; Risk; Science; Science (multidisciplinary); Synergistic effect
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-43064-x

Alcohol-related liver disease (ARLD) represents a major public health burden. Identification of high-risk individuals would allow efficient targeting of public health interventions. Here, we show significant interactions between pattern of drinking, genetic predisposition (polygenic risk score, PRS) and diabetes mellitus, and risk of incident ARLD, in 312,599 actively drinking adults in UK Biobank. Binge and heavy binge drinking significantly increase the risk of alcohol-related cirrhosis (ARC), with higher genetic predisposition further amplifying the risk. Further, we demonstrate a pronounced interaction between heavy binge drinking and high PRS, resulting in a relative excess risk due to interaction (RERI) of 6.07. Diabetes consistently elevates ARC risk across all drinking and PRS categories, and showed significant interaction with both binge patterns and genetic risk. Overall, we demonstrate synergistic effects of binge drinking, genetics, and diabetes on ARC, with potential to identify high-risk individuals for targeted interventions. Deaths from alcohol-related liver disease have sharply increased following the Covid-19 pandemic. Here, the authors show that binge-pattern alcohol consumption, genetic factors and the presence of diabetes mellitus confer the greatest risk, allowing targeted interventions for high-risk individuals.