Identifying Genetic Variation for Alcohol Dependence

Researchers are using various strategies to identify the genes that may be associated with alcoholism. The initial efforts primarily relied on candidate gene and linkage studies; more recently, however, modern advances in genotyping have resulted in widespread use of genome-wide association studies for alcohol dependence. The key findings of the earlier studies were that variations (i.e., polymorphisms) in the DNA sequences of the genes encoding alcohol dehydrogenase 1B (i.e., the ADH1B gene), aldehyde dehydrogenase 2 (i.e., the ALDH2 gene), and other alcohol-metabolizing enzymes mediate the risk for alcoholism; moreover, these polymorphisms also have an impact on the risk of alcohol-related cancers, such as esophageal cancer. In addition, a gene encoding one of the receptors for the neurotransmitter γ-aminobutyric acid (GABA) known as GABRA2 seems to have a role in the development of alcohol dependence. Genome-wide association studies now offer a host of emerging opportunities, as well as challenges, for discovering the genetic etiology of alcohol dependence and for unveiling new treatment strategies.

• Publication year

  2012

• Venue

  Alcohol research : current reviews

• Publication date

  Unknown publication date

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.35946/arcr.v34.3.02PMID 23134043PMCID 3662475
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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• Strong association of the alcohol dehydrogenase 1B gene (ADH1B) with alcohol dependence and alcohol-induced medical diseases.

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• ADH1B is associated with alcohol dependence and alcohol consumption in populations of European and African ancestry

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• Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption

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• A quantitative-trait genome-wide association study of alcoholism risk in the community: findings and implications.

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  2010cited by this paper
• Relationship between genetic polymorphisms of ALDH2 and ADH1B and esophageal cancer risk: a meta-analysis.

  2010cited by this paper
• Genome-wide association study of alcohol dependence implicates a region on chromosome 11.

  2010cited by this paper
• Altering the relative abundance of GABA A receptor subunits changes GABA- and ethanol-responses in Xenopus oocytes.

  2009cited by this paper
• Ancestry informative marker sets for determining continental origin and admixture proportions in common populations in America

  2009cited by this paper
• Potential etiologic and functional implications of genome-wide association loci for human diseases and traits

  2009cited by this paper
• The Alcohol Flushing Response: An Unrecognized Risk Factor for Esophageal Cancer from Alcohol Consumption

  2009cited by this paper
• Genome-wide association study of alcohol dependence.

  2009cited by this paper
• Associations of ADH and ALDH2 gene variation with self report alcohol reactions, consumption and dependence: an integrated analysis.

  2009cited by this paper
• GABA-A2 receptor subunit gene (GABRA2) polymorphisms and risk for alcohol dependence.

  2008cited by this paper
• The role of GABRA2 in alcohol dependence, smoking, and illicit drug use in an Australian population sample.

  2008cited by this paper
• Multiple ADH genes are associated with upper aerodigestive cancers

  2008cited by this paper
• Targeted deletion of the GABRA2 gene encoding alpha2-subunits of GABA(A) receptors facilitates performance of a conditioned emotional response, and abolishes anxiolytic effects of benzodiazepines and barbiturates.

  2008cited by this paper
• Human gamma-aminobutyric acid A receptor alpha2 gene moderates the acute effects of alcohol and brain mRNA expression.

  2008cited by this paper
• The Genetics of Alcohol Metabolism: Role of Alcohol Dehydrogenase and Aldehyde Dehydrogenase Variants

  2007cited by this paper
• Prevalence, correlates, disability, and comorbidity of DSM-IV alcohol abuse and dependence in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions.

  2007cited by this paper
• Evidence of positive selection on a class I ADH locus.

  2007cited by this paper
• Association of alcohol dehydrogenase genes with alcohol dependence: a comprehensive analysis.

  2006cited by this paper
• ADH4 Gene Variation is Associated with Alcohol Dependence and Drug Dependence in European Americans: Results from HWD Tests and Case–Control Association Studies

  2006cited by this paper
• Linkage disequilibrium, haplotype and association studies of a chromosome 4 GABA receptor gene cluster: Candidate gene variants for addictions

  2006cited by this paper
• The genetics of alcohol dependence

  2006cited by this paper
• Association between alcoholism and gamma-amino butyric acid alpha2 receptor subtype in a Russian population.

  2005cited by this paper
• Actual causes of death in the United States, 2000.

  2004cited by this paper
• Variations in GABRA2, encoding the alpha 2 subunit of the GABA(A) receptor, are associated with alcohol dependence and with brain oscillations.

  2004cited by this paper
• gamma-Aminobutyric acid A receptor subunit mutant mice: new perspectives on alcohol actions.

  2004cited by this paper
• α2‐γ‐Aminobutyric acid (GABA)A receptors are the molecular substrates mediating precipitation of narcosis but not of sedation by the combined use of diazepam and alcohol in vivo

  2003cited by this paper
• Evaluation of the glutamate decarboxylase genes Gad1 and Gad2 as candidate genes for acute ethanol withdrawal severity in mice.

  2003cited by this paper
• Animal models of alcoholism: neurobiology of high alcohol-drinking behavior in rodents.

  1998cited by this paper
• Alcohol and aldehyde dehydrogenase genotypes and alcoholism in Chinese men.

  1991cited by this paper
• Ethnic Differences in Alcohol Sensitivity

  1972cited by this paper

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• Deep sequencing of candidate genes identified 14 variants associated with smoking abstinence in an ethnically diverse sample

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• Developmental genetic effects on externalizing behavior and alcohol use: Examination across two longitudinal samples.

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  2021cites this paper
• Brain Function and Substance Use Disorders

  2020cites this paper
• Diagnosis of Substance Use Disorders

  2020cites this paper
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  2020cites this paper
• Genetic Influence on Substance Use Disorders

  2020cites this paper
• Behavioral, Cognitive, and Social Factors Promoting SUD

  2020cites this paper
• Tranquilizers and Sedative Use Disorders

  2020cites this paper
• Opioid Use Disorders

  2020cites this paper
• Use Disorders of Cocaine and Methamphetamine

  2020cites this paper
• The Biopsychosocial Perspective and Research Methods for Investigation of Substance Use Disorders

  2020cites this paper
• Cannabis Use Disorders

  2020cites this paper
• Psychiatric Disorders, Personality, and Developmental Factors

  2020cites this paper
• Substance Use Disorders

  2020cites this paper
• Genetic variant rs72613567 of HSD17B13 gene reduces alcohol‐related liver disease risk in Chinese Han population

  2020cites this paper
• Psychopharmacology

  2020cites this paper
• Diverse types of genomic evidence converge on alcohol use disorder risk genes

  2020cites this paper
• Recent Advances in Genetic Studies of Alcohol Use Disorders

  2020cites this paper
• Alcohol Use Disorders

  2020cites this paper
• Tobacco Use and Nicotine Addiction

  2020cites this paper
• Treatment of Substance Use Disorders

  2020cites this paper
• References

  2020cites this paper
• Smart Healthcare Systems and Precision Medicine.

  2019cites this paper
• Genome-Wide Systems Genetics of Alcohol Consumption and Dependence

  2019cites this paper
• Unpacking genetic risk pathways for college student alcohol consumption: The mediating role of impulsivity.

  2019cites this paper
• The mediational role of affect regulation on the relation between attachment and alcohol use in college students

  2019cites this paper
• Alcohol

  2019cites this paper
• Analysis of whole genome-transcriptomic organization in brain to identify genes associated with alcoholism

  2018cites this paper
• Familial alcohol supply, adolescent drinking and early alcohol onset in 45 low and middle income countries.

  2018cites this paper
• Alcohol drinking and problems in young populations: the challenge in Asia

  2018cites this paper
• Infrastructure and Career Opportunities in Addiction Science : The Emergence of an Interdisciplinary Field

  2017cites this paper
• Genetics of Liver Diseases

  2017cites this paper
• Alcohol, microbiome, life style influence alcohol and non-alcoholic organ damage.

  2017cites this paper
• Gene expression profiling in the human alcoholic brain.

  2017cites this paper
• Alcohol and nicotine codependence-associated DNA methylation changes in promoter regions of addiction-related genes

  2017cites this paper
• Review: DNA methylation and alcohol use disorders Progress and challenges

  2017cites this paper
• Genome-wide association study of Alcohol Use Disorder Identification Test (AUDIT) scores in 20,328 research participants of European ancestry

  2017cites this paper
• Genetic studies of alcohol dependence in the context of the addiction cycle

  2017cites this paper
• Opioid Use Disorders.

  2016cites this paper
• Causal Role of Alcohol Consumption in an Improved Lipid Profile: The Atherosclerosis Risk in Communities (ARIC) Study

  2016cites this paper
• Work stress and alcohol use: developing and testing a biphasic self-medication model

  2016cites this paper
• Genetics of Alcoholic Liver Disease

  2015cites this paper
• Relations of negative and positive work experiences to employee alcohol use: testing the intervening role of negative and positive work rumination.

  2015cites this paper
• Candidate Gene–Environment Interaction Research

  2015cites this paper
• Alcohol Dependence Genetics: Lessons Learned From Genome-Wide Association Studies (GWAS) and Post-GWAS Analyses.

  2015cites this paper
• Differentially co-expressed genes in postmortem prefrontal cortex of individuals with alcohol use disorders: influence on alcohol metabolism-related pathways

  2014cites this paper
• ACADEMIC SUCCESS OF FIRST YEAR STUDENTS: THE EFFECTS OF ALCOHOL EXPECTANCY AND ACADEMIC SELF-EFFICACY

  2014cites this paper
• Red ginseng relieves the effects of alcohol consumption and hangover symptoms in healthy men: a randomized crossover study.

  2014cites this paper
• Alcohol consumption mediates the relationship between ADH1B and DSM-IV alcohol use disorder and criteria.

  2014cites this paper
• Replication Study of ESCC Susceptibility Genetic Polymorphisms Locating in the ADH1B-ADH1C-ADH7 Cluster Identified by GWAS

  2014cites this paper
• Alcoholism on the American Stage: De- Stigmatizing Socially Constructed Depictions of the Alcoholic through Performance

  2013cites this paper
• The Separate and Combined Effects of Heredity and Environment Predicting Alcohol Use Disorder Symptoms and Antisocial Personality Disorder Symptoms

  2013cites this paper
• The Disease Concept

  1967cites this paper