@article{discovery10184237, number = {1}, month = {December}, journal = {Nature Communications}, title = {Binge-pattern alcohol consumption and genetic risk as determinants of alcohol-related liver disease}, year = {2023}, publisher = {Springer Science and Business Media LLC}, note = {This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.}, volume = {14}, keywords = {Alcoholic liver disease, Epidemiology, Genome-wide association studies}, abstract = {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.}, author = {Ding, Chengyi and Ng Fat, Linda and Britton, Annie and Im, Pek Kei and Lin, Kuang and Topiwala, Anya and Li, Liming and Chen, Zhengming and Millwood, Iona Y and Bell, Steven and Mehta, Gautam}, url = {http://dx.doi.org/10.1038/s41467-023-43064-x} }