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

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

Nat Commun. 2023 Dec 14;14(1):8041. doi: 10.1038/s41467-023-43064-x.

Authors

Chengyi Ding^#¹, Linda Ng Fat^#², Annie Britton², Pek Kei Im³, Kuang Lin³, Anya Topiwala⁴, Liming Li^{5

6

7}, Zhengming Chen^{3

8}, Iona Y Millwood^{3

8}, Steven Bell^{9

10}, Gautam Mehta^{11

12

13}

Affiliations

¹ Division of Psychiatry, University College London, London, UK.
² Research Department of Epidemiology and Public Health, University College London, London, UK.
³ Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.
⁴ Big Data Institute, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
⁵ Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.
⁶ Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, China.
⁷ Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing, China.
⁸ Medical Research Council Population Health Research Unit (MRC PHRU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.
⁹ Precision Breast Cancer Institute, Department of Oncology, University of Cambridge, Cambridge, UK. scb81@medschl.cam.ac.uk.
¹⁰ Cancer Research UK Cambridge Centre, Li Ka Shing Centre, University of Cambridge, Cambridge, UK. scb81@medschl.cam.ac.uk.
¹¹ Institute for Liver and Digestive Health, University College London, London, UK. gautam.mehta@ucl.ac.uk.
¹² Roger Williams Institute of Hepatology, Foundation for Liver Research, London, UK. gautam.mehta@ucl.ac.uk.
¹³ Royal Free London NHS Foundation Trust, London, UK. gautam.mehta@ucl.ac.uk.

^# Contributed equally.

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.

MeSH terms

Adult
Alcohol Drinking / adverse effects
Alcohol Drinking / genetics
Binge Drinking* / epidemiology
Binge Drinking* / genetics
Diabetes Mellitus*
Ethanol
Genetic Predisposition to Disease
Humans
Liver Diseases*

Substances

Ethanol

Abstract

MeSH terms

Substances

Grants and funding