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Recent Efforts to Dissect the Genetic Basis of Alcohol Use and Abuse

Published:September 25, 2019DOI:https://doi.org/10.1016/j.biopsych.2019.09.011

      Abstract

      Alcohol use disorder (AUD) is defined by several symptom criteria, which can be dissected further at the genetic level. Over the past several years, our understanding of the genetic factors influencing alcohol use and abuse has progressed tremendously; numerous loci have been implicated in different aspects of alcohol use. Previously known associations with alcohol-metabolizing enzymes (ADH1B, ALDH2) have been replicated definitively. In addition, novel associations with loci containing the genes KLB, GCKR, CRHR1, and CADM2 have been reported. Downstream analyses have leveraged these genetic findings to reveal important relationships between alcohol use behaviors and both physical and mental health. AUD and aspects of alcohol misuse have been shown to overlap strongly with psychiatric disorders, whereas aspects of alcohol consumption have shown stronger links to metabolism. These results demonstrate that the genetic architecture of alcohol consumption only partially overlaps with the genetics of clinically defined AUD. We discuss the limitations of using quantitative measures of alcohol use as proxy measures for AUD, and we outline how future studies will require careful phenotype harmonization to properly capture the genetic liability to AUD.

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      Linked Article

      • Advancing Alcohol Genetics Research: One Genome-wide Association Study at a Time and Beyond
        Biological PsychiatryVol. 87Issue 7
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          Alcohol use behaviors are highly complex and heterogeneous. They are all influenced by genetic factors. Genome-wide association studies (GWASs) have been widely used to dissect the genetic architecture of psychiatric disorders, including alcohol-related traits. Initially, there was skepticism on the potential contribution of GWASs in the field of psychiatry. Most first-wave GWAS studies were, we know in hindsight, greatly underpowered and failed to identify risk loci associated with psychiatric disorders.
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