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The genetics of alcohol dependence and alcohol-related liver disease

Stickel, F; Moreno, C; Hampe, J; Morgan, MY; (2017) The genetics of alcohol dependence and alcohol-related liver disease. Journal of Hepatology , 66 (1) pp. 195-211. 10.1016/j.jhep.2016.08.011. Green open access

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Abstract

The susceptibility to developing alcohol dependence and significant alcohol-related liver injury is determined by a number of constitutional, environmental and genetic factors, although the nature and level of interplay between them remains unclear. The familiality and heritability of alcohol dependence is well-documented but, to date, no strong candidate genes conferring increased risk have emerged, although variants in alcohol dehydrogenase and acetaldehyde dehydrogenase have been shown to confer protection, predominantly in individuals of East Asian ancestry. Population contamination with confounders such as drug co-dependence and psychiatric and physical co-morbidity may explain the essentially negative genome-wide association studies in this disorder. The familiality and hereditability of alcohol-related cirrhosis is not as well-documented but three strong candidate genes PNPLA3, TM6SF2 and MBOAT7, have been identified. The mechanisms by which variants in these genes confer risk and the nature of the functional interplay between them remains to be determined but, when elucidated, will undoubtedly increase our understanding of the pathophysiology of this disease. The way in which this genetic information could potentially inform patient management has yet to be determined and tested.

Type: Article
Title: The genetics of alcohol dependence and alcohol-related liver disease
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.jhep.2016.08.011
Publisher version: http://dx.doi.org/10.1016/j.jhep.2016.08.011
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Alcohol dehydrogenase, Alcohol dependence, Alcohol metabolism, Alcohol use disorders, Alcoholic, Alcoholism, Aldehyde oxidoreductases, Ethanol, Genome-wide association study, Heritability estimates, Liver Cirrhosis, Phenotypic variability, Substance-related disorders, Alcohol Dehydrogenase, Alcoholism, Gene-Environment Interaction, Genetic Predisposition to Disease, Humans, Liver Diseases, Alcoholic, Polymorphism, Genetic, Protective Factors
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inst for Liver and Digestive Hlth
URI: http://discovery.ucl.ac.uk/id/eprint/10048560
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