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Genetics and alcoholism

Abstract

Alcohol is widely consumed; however, excessive use creates serious physical, psychological and social problems and contributes to the pathogenesis of many diseases. Alcohol use disorders (that is, alcohol dependence and alcohol abuse) are maladaptive patterns of excessive drinking that lead to serious problems. Abundant evidence indicates that alcohol dependence (alcoholism) is a complex genetic disease, with variations in a large number of genes affecting a person's risk of alcoholism. Some of these genes have been identified, including two genes involved in the metabolism of alcohol (ADH1B and ALDH2) that have the strongest known affects on the risk of alcoholism. Studies continue to reveal other genes in which variants affect the risk of alcoholism or related traits, including GABRA2, CHRM2, KCNJ6 and AUTS2. As more variants are analysed and studies are combined for meta-analysis to achieve increased sample sizes, an improved picture of the many genes and pathways that affect the risk of alcoholism will be possible.

Key Points

  • Alcohol dependence is a common, complex genetic disease, with many variants in numerous genes contributing to the risk of developing this disorder

  • Genes involved in alcohol metabolism have strong effects on risk; functional variants of ADH1B and ALDH2 exist that protect against alcoholism, with ORs of 0.2–0.4

  • Several other genes, including GABRA2 and CHRM2, have been associated with alcohol dependence in many studies; evidence suggests numerous other genes affect the disease and traits associated with it

  • As samples of increased size are assembled for meta-analyses and an extended range of alleles are tested, the roles of many additional genes will probably be uncovered

  • Excessive alcohol consumption, particularly binge drinking, contributes to many other diseases, including cirrhosis and cancers of the upper aerodigestive tract, colon, rectum and liver

  • Genes that alter how much alcohol a person consumes and how often affect the risk of many of these diseases

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Figure 1: Major pathway of alcohol metabolism.

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Acknowledgements

Related work in the authors' laboratories is supported by grants from the National Institutes of Health, AA008401, AA006460, AA020892, AA007611.

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Correspondence to Howard J. Edenberg.

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Edenberg, H., Foroud, T. Genetics and alcoholism. Nat Rev Gastroenterol Hepatol 10, 487–494 (2013). https://doi.org/10.1038/nrgastro.2013.86

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