eprintid: 10184237 rev_number: 7 eprint_status: archive userid: 699 dir: disk0/10/18/42/37 datestamp: 2023-12-20 15:44:29 lastmod: 2024-10-31 20:16:22 status_changed: 2023-12-20 15:44:29 type: article metadata_visibility: show sword_depositor: 699 creators_name: Ding, Chengyi creators_name: Ng Fat, Linda creators_name: Britton, Annie creators_name: Im, Pek Kei creators_name: Lin, Kuang creators_name: Topiwala, Anya creators_name: Li, Liming creators_name: Chen, Zhengming creators_name: Millwood, Iona Y creators_name: Bell, Steven creators_name: Mehta, Gautam title: Binge-pattern alcohol consumption and genetic risk as determinants of alcohol-related liver disease ispublished: pub subjects: RFH divisions: UCL divisions: B02 divisions: C10 divisions: D17 divisions: G91 keywords: Alcoholic liver disease, Epidemiology, Genome-wide association studies 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/. 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. date: 2023-12-14 date_type: published publisher: Springer Science and Business Media LLC official_url: http://dx.doi.org/10.1038/s41467-023-43064-x oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 2133995 doi: 10.1038/s41467-023-43064-x pii: 10.1038/s41467-023-43064-x lyricists_name: Mehta, Gautam lyricists_id: GMEHT72 actors_name: Flynn, Bernadette actors_id: BFFLY94 actors_role: owner funding_acknowledgements: 216462/Z/19/Z [Wellcome Trust (Wellcome)] full_text_status: public publication: Nature Communications volume: 14 number: 1 article_number: 8041 event_location: England citation: Ding, Chengyi; Ng Fat, Linda; Britton, Annie; Im, Pek Kei; Lin, Kuang; Topiwala, Anya; Li, Liming; ... Mehta, Gautam; + view all <#> 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; - view fewer <#> (2023) Binge-pattern alcohol consumption and genetic risk as determinants of alcohol-related liver disease. Nature Communications , 14 (1) , Article 8041. 10.1038/s41467-023-43064-x <https://doi.org/10.1038/s41467-023-43064-x>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10184237/1/s41467-023-43064-x.pdf