title: The genetics of alcohol dependence and alcohol-related liver disease.
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.
authors: Department of Gastroenterology and Hepatology, University Hospital of Zurich, Switzerland. Electronic address: Felix.stickel@ikp.unibe.ch.
authors: Felix
authors: F
authors: Stickel
authors: 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.
authors: Christophe
authors: C
authors: Moreno
authors: Medical Department 1, University Hospital Dresden, TU Dresden, Germany.
authors: Jochen
authors: J
authors: Hampe
authors: UCL Institute for Liver & Digestive Health, Division of Medicine, Royal Free Campus, University College London, UK.
authors: Marsha Y
authors: MY
authors: Morgan
mesh_terms: D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000437:Alcoholism / Q000235:genetics*; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D008108:Liver Diseases, Alcoholic / Q000235:genetics*; D011110:Polymorphism, Genetic; D065840:Protective Factors
chemical_list: D000426:Alcohol Dehydrogenase
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