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

Chengyi Ding; Linda Ng Fat; Annie Britton; Pek Kei Im; Kuang Lin; Anya Topiwala; Liming Li; Zhengming Chen; Iona Y. Millwood; Steven Bell; Gautam Mehta

doi:10.1038/s41467-023-43064-x

Nature Communications (Dec 2023)

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

Chengyi Ding,
Linda Ng Fat,
Annie Britton,
Pek Kei Im,
Kuang Lin,
Anya Topiwala,
Liming Li,
Zhengming Chen,
Iona Y. Millwood,
Steven Bell,
Gautam Mehta

Affiliations

Chengyi Ding: Division of Psychiatry, University College London
Linda Ng Fat: Research Department of Epidemiology and Public Health, University College London
Annie Britton: Research Department of Epidemiology and Public Health, University College London
Pek Kei Im: Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford
Kuang Lin: Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford
Anya Topiwala: Big Data Institute, Nuffield Department of Population Health, University of Oxford
Liming Li: Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center
Zhengming Chen: Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford
Iona Y. Millwood: Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford
Steven Bell: Precision Breast Cancer Institute, Department of Oncology, University of Cambridge
Gautam Mehta: Institute for Liver and Digestive Health, University College London

DOI: https://doi.org/10.1038/s41467-023-43064-x
Journal volume & issue: Vol. 14, no. 1
pp. 1 – 8

Abstract

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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.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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