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The genetics of alcohol dependence and alcohol-related liver disease

  • Author Footnotes
    † These authors contributed equally as joint first authors.
    Felix Stickel
    Correspondence
    Corresponding author. Address: Department of Gastroenterology and Hepatology, University Hospital of Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland. Tel.: +41 31 335 7816; fax: +41 31 335 3519.
    Footnotes
    † These authors contributed equally as joint first authors.
    Affiliations
    Department of Gastroenterology and Hepatology, University Hospital of Zurich, Switzerland
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  • Author Footnotes
    † These authors contributed equally as joint first authors.
    Christophe Moreno
    Footnotes
    † These authors contributed equally as joint first authors.
    Affiliations
    Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium

    Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium
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  • Jochen Hampe
    Affiliations
    Medical Department 1, University Hospital Dresden, TU Dresden, Germany
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  • Marsha Y. Morgan
    Affiliations
    UCL Institute for Liver & Digestive Health, Division of Medicine, Royal Free Campus, University College London, UK
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  • Author Footnotes
    † These authors contributed equally as joint first authors.
Published:August 27, 2016DOI:https://doi.org/10.1016/j.jhep.2016.08.011

      Summary

      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.

      Keywords

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