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 () and Gautam Mehta ()
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Chengyi Ding: University College London
Linda Ng Fat: University College London
Annie Britton: University College London
Pek Kei Im: University of Oxford
Kuang Lin: University of Oxford
Anya Topiwala: University of Oxford
Liming Li: Peking University Health Science Center
Zhengming Chen: University of Oxford
Iona Y. Millwood: University of Oxford
Steven Bell: University of Cambridge
Gautam Mehta: University College London

Nature Communications, 2023, vol. 14, issue 1, 1-8

Abstract: 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
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DOI: 10.1038/s41467-023-43064-x

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