Genetics and alcoholism

Edenberg, Howard J.; Foroud, Tatiana

doi:10.1038/nrgastro.2013.86

Cited by 154 publications

(152 citation statements)

References 79 publications

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“…Not surprisingly, the SNPs in the genes encoding the alcohol metabolizing enzymes are among the common variants with the largest effects on AUD risk. The associations found in the alcohol-metabolizing enzyme genes represent the most consistent overall finding for GWAS of alcohol dependence to date and these results replicate findings from candidate gene and linkage studies which have found similar associations with these enzymes (Edenberg and Foroud, 2013). However, these results were somewhat discouraging because it was widely predicted that the GWAS-era would revolutionize our understanding of the genetics of complex traits including alcohol dependence by uncovering many novel and unexpected common genetic variants for alcohol dependence that have eluded linkage and candidate gene association studies.…”

Section: Genome-wide Association Studies Of Alcohol Dependencesupporting

confidence: 85%

Genetic studies of alcohol dependence in the context of the addiction cycle

et al. 2017

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Family, twin and adoption studies demonstrate clearly that alcohol dependence and alcohol use disorders are phenotypically complex and heritable. The heritability of alcohol use disorders is estimated at approximately 50–60% of the total phenotypic variability. Vulnerability to alcohol use disorders can be due to multiple genetic or environmental factors or their interaction which gives rise to extensive and daunting heterogeneity. This heterogeneity makes it a significant challenge in mapping and identifying the specific genes that influence alcohol use disorders. Genetic linkage and (candidate gene) association studies have been used now for decades to map and characterize genomic loci and genes that underlie the genetic vulnerability to alcohol use disorders. These approaches have been moderately successful in identifying several genes that contribute to the complexity of alcohol use disorders. Recently, genome-wide association studies have become one of the major tools for identifying genes for alcohol use disorders by examining correlations between millions of common single-nucleotide polymorphisms with diagnosis status. Genome-wide association studies are just beginning to uncover novel biology; however, the functional significance of results remains a matter of extensive debate and uncertainty. In this review, we present a select group of genome-wide association studies of alcohol dependence, as one example of a way to generate functional hypotheses, within the addiction cycle framework. This analysis may provide novel directions for validating the functional significance of alcohol dependence candidate genes. This article is part of the Special Issue entitled “Alcoholism”.

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Section: Genome-wide Association Studies Of Alcohol Dependencesupporting

confidence: 85%

Genetic studies of alcohol dependence in the context of the addiction cycle

et al. 2017

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“…Epidemiological evidence indicates that alcoholic liver injury from harmful alcohol consumption is one of leading risk factors for the occurrence of liver diseases and many other diseases [4,5]. Therefore, a meaningful management strategy that identifies effective natural compounds for alcohol consumers to prevent or slow down the progression of alcoholic liver injury in the early stage would be beneficial.…”

Section: Introductionmentioning

confidence: 99%

Dendrobium huoshanense polysaccharide prevents ethanol-induced liver injury in mice by metabolomic analysis

Wang

Luo

Chen

et al. 2015

International Journal of Biological Macromolecules

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“…A genetic link to AUDs has been well established, yet, with the exception of the major alcohol metabolizing enzymes, the underlying molecular basis of this link remains mostly a mystery (Edenberg & Foroud, 2013). This is for a variety of reasons, including small effect size of individual genes and clinical heterogeneity.…”

Section: Discussionmentioning

confidence: 99%

Atp1a2 contributes modestly to alcohol-related behaviors

Gritz

Larson

Radcliffe

2016

Alcohol

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Atp1a2 has been previously studied for anxiety, learning and motor function disorders, and fear. Since Atp1a2 has been shown to be involved in anxiety and this behavior is a known risk factor for developing alcoholism, we have been investigating Atp1a2 for its potential role in responses to alcohol. This study utilized Atp1a2 knockout mice; Atp1a2 heterozygous mice, with half the amount of protein compared to wild-type mice, were used because Atp1a2 homozygous null mice die shortly after birth. The alcohol-related behavioral experiments performed were loss of righting reflex (LORR), acute alcohol withdrawal measured by handling-induced convulsions (HIC), drinking in the dark (DID), open-field activity (OFA), and elevated plus-maze (EPM). LORR was a 2-day test that measures acute alcohol sensitivity, and rapid and acute functional tolerance (AFT). HIC was a 3-day test to measure alcohol withdrawal, DID was a 4-day test which measures voluntary alcohol consumption, and OFA and EPM measured anxiety with alcohol exposure. The effect of genotype on alcohol metabolism was also examined. There was a genotype effect on rate of alcohol metabolism, but only in males. There was no effect on alcohol withdrawal severity. The Atp1a2 heterozygous mice consumed more alcohol than wild-type mice in the DID test, although only in males. In addition, only males were observed to show rapid tolerance in the LORR test while only female heterozygous mice showed a pretreatment effect on AFT. Alcohol exposure had a greater anxiolytic effect in the heterozygous mice compared to wild-type mice, although, again, there were sex effects with only males showing the effect in OFA and only females in the EPM. Although the behavioral results were mixed, there does appear to be a connection between anxiety and alcohol. Overall, the results suggest that Atp1a2 does contribute to alcohol-related behaviors, although the effect is modest with a clear dependence on sex.

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Genetics and alcoholism

Cited by 154 publications

References 79 publications

Genetic studies of alcohol dependence in the context of the addiction cycle

Genetic studies of alcohol dependence in the context of the addiction cycle

Dendrobium huoshanense polysaccharide prevents ethanol-induced liver injury in mice by metabolomic analysis

Atp1a2 contributes modestly to alcohol-related behaviors

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