TY  - JOUR
VL  - 14
AV  - public
Y1  - 2023/12/14/
TI  - Binge-pattern alcohol consumption and genetic risk as determinants of alcohol-related liver disease
IS  - 1
N1  - 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/.
UR  - http://dx.doi.org/10.1038/s41467-023-43064-x
PB  - Springer Science and Business Media LLC
N2  - 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.
ID  - discovery10184237
A1  - Ding, Chengyi
A1  - Ng Fat, Linda
A1  - Britton, Annie
A1  - Im, Pek Kei
A1  - Lin, Kuang
A1  - Topiwala, Anya
A1  - Li, Liming
A1  - Chen, Zhengming
A1  - Millwood, Iona Y
A1  - Bell, Steven
A1  - Mehta, Gautam
KW  - Alcoholic liver disease
KW  -  Epidemiology
KW  -  Genome-wide association studies
JF  - Nature Communications
ER  -