Genetics of Addictions
Section snippets
Genetics of alcohol dependence
Alcohol dependence is a complex disease, with genetic and environmental risk factors. Alcohol dependence (commonly known as alcoholism) necessarily has a strong environmental component because exposure to and consumption of alcohol is required for the disorder. But, there is a substantial heritable component to the risk for alcoholism. Among first-degree relatives of alcohol-dependent individuals, the risk of alcohol dependence is 3 to 8 times the baseline population risk.9
Alcohol dependence
Nicotine dependence
The conceptualization of the different stages of smoking is helpful in understanding the varying environmental and genetic contributions to each step in the development of smoking behaviors. To better understand smoking behavior, it is compartmentalized into (1) initiation (the period during which subjects smoke for the first time and experiment with smoking), (2) regular smoking (defined as subjects having smoked at least 100 cigarettes during their lifetime), and (3) nicotine dependence (a
Cocaine dependence
It is estimated that approximately 2.1% of US residents have used cocaine in the past month, the second most prevalent nonmedical drug to marijuana.49 Similar to nicotine and alcohol dependence, cocaine dependence has a strong component of heritability: siblings of cocaine-dependent probands had an estimated relative risk of 1.8 of developing cocaine dependence compared with probands without cocaine-dependent siblings.50 Because of the hypothesis that common genetic factors may lead to
Genetic association of substance dependence with other mental illness
The tendency of subjects with mental illness to use substances has been extensively discussed. A traditional hypothesis was that substance use is a means of self-medicating and dependence is therefore ‘caused’ by mental illness. On the contrary, data have been published that smoking precedes the diagnosis of mental illness and may contribute to the disorder. For example, there is an increased risk of first onset major depression in smokers53, 54, 55, 56 and an increase in depressive symptoms in
Summary
Addictions are common heritable disorders with multiple psychiatric and medical comorbidities. Persons with substance abuse are approximately twice as likely to suffer psychiatric morbidities as those without substance abuse, and have an increased risk of using inpatient and emergency facilities. In addition, public mental health clients had a decreased life span of 13 to 30 years; most deaths are caused by heart disease and cancer. Cigarette smoking is therefore the largest modifiable risk
References (63)
- et al.
Possible protective role against alcoholism for aldehyde dehydrogenase isozyme deficiency in Japan
Lancet
(1982) - et al.
Interaction between the functional polymorphisms of the alcohol-metabolism genes in protection against alcoholism
Am J Hum Genet
(1999) - et al.
Aldehyde dehydrogenase genotypes in Japanese alcoholics
Lancet
(1994) Alcohol dehydrogenase and alcohol dependence: variation in genotype-associated risk between populations
Am J Hum Genet
(2002)- et al.
Variations in GABRA2, encoding the alpha 2 subunit of the GABA(A) receptor, are associated with alcohol dependence and with brain oscillations
Am J Hum Genet
(2004) - et al.
GABA-A2 receptor subunit gene (GABRA2) polymorphisms and risk for alcohol dependence
J Psychiatr Res
(2008) - et al.
Ethanol and the GABA receptor complex: studies with the partial inverse benzodiazepine receptor agonist Ro 15-4513
Pharmacol Biochem Behav
(1988) - et al.
Bidirectional effects of GABAergic agonists and antagonists on maintenance of voluntary ethanol intake in rats
Pharmacol Biochem Behav
(1993) - et al.
Smoking cessation and variations in nicotinic acetylcholine receptor subunits alpha-5, alpha-3, and beta-4 genes
Biol Psychiatry
(2009) - et al.
A risk allele for nicotine dependence in CHRNA5 is a protective allele for cocaine dependence
Biol Psychiatry
(2008)
Cigarette smoking, major depression, and other psychiatric disorders among adolescents
J Am Acad Child Adolesc Psychiatry
Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study
Lancet
Unipolar depressive disorders have a common genotype
J Affect Disord
Task Force on DSM-IV. Diagnostic and statistical manual of mental disorders: DSM-IV-TR
Nicotine dependence and psychiatric disorders in the United States: results from the national epidemiologic survey on alcohol and related conditions
Arch Gen Psychiatry
Comorbidity of mental disorders with alcohol and other drug abuse. Results from the Epidemiologic Catchment Area (ECA) Study
JAMA
Treatment for co-occurring mental and substance use disorders in five state Medicaid programs
Psychiatr Serv
Smoking and mental illness: a population-based prevalence study
JAMA
Congruencies in increased mortality rates, years of potential life lost, and causes of death among public mental health clients in eight states
Prev Chronic Dis
Morbidity and mortality in people with serious mental illness
The relationship between smoking and suicidal behavior, comorbidity, and course of illness in bipolar disorder
J Clin Psychiatry
Genome-wide search for genes affecting the risk for alcohol dependence
Am J Med Genet
Ethnic differences in alcohol sensitivity
Science
Genetic studies on alcohol-metabolizing enzymes: detection of isozymes in human hair roots
Enzyme
The genetics of alcohol metabolism: role of alcohol dehydrogenase and aldehyde dehydrogenase variants
Alcohol Res Health
The evolution and population genetics of the ALDH2 locus: random genetic drift, selection, and low levels of recombination
Ann Hum Genet
Meta-analyses of ALDH2 and ADH1B with alcohol dependence in Asians
Psychol Bull
Alcohol and aldehyde dehydrogenase genotypes and alcoholism in Chinese men
Am J Hum Genet
Association of GABRA2 with drug dependence in the collaborative study of the genetics of alcoholism sample
Behav Genet
Allelic and haplotypic association of GABRA2 with alcohol dependence
Am J Med Genet B Neuropsychiatr Genet
Confirmation of association of the GABRA2 gene with alcohol dependence by subtype-specific analysis
Psychiatr Genet
Cited by (3)
A haplotype analysis is consistent with the role of functional HTR1B variants in alcohol dependence
2012, Drug and Alcohol DependenceCitation Excerpt :Although the results of genome-wide association studies for alcoholism have not revealed strong findings (Edenberg et al., 2010; Treutlein et al., 2009), the candidate gene approach may still provide significant findings since the polymorphisms and haplotypes studied may be carefully chosen based on a hypothesis-oriented approach. Although there is strong evidence that alcohol metabolism-related genes play a part in alcohol dependence, these genes account for only a small proportion of the genetic variance (Hartz and Bierut, 2010; Huang, 2010; Ösby et al., 2010). Therefore, several efforts to identify other genetic variants associated with the susceptibility to alcoholism have been focusing on genes involved in the neurotransmitter regulation (Huang, 2010; McHugh et al., 2010).
MAOA uVNTR Polymorphism Influence on Older Adults Diagnosed with Diabetes Mellitus/Systemic Arterial Hypertension
2023, Journal of Aging ResearchInforming prevention and intervention policy using genetic studies of resistance
2018, Prevention Science
Disclosures: Dr L Bierut is listed as an inventor on a patent “Markers of Addiction” (US 20070258898), covering the use of certain single nucleotide polymorphisms in determining the diagnosis, prognosis, and treatment of addiction. Dr Bierut acted as a consultant for Pfizer, Inc in 2008.
Funding support: Collaborative Genetic Study of Nicotine Dependence P01 CA89392 (National Cancer Institute), Study of Addiction: Genetics and Environment U01 HG004422 (National Human Genome Research Institute), Case Control Candidate Gene Study of Addiction R01 DA19963 (National Institute on Drug Abuse), Human Genetics of Addiction: A Study of Common and Specific Factors K02 DA021237 (National Institute on Drug Abuse), Collaborative Study on the Genetics of Alcoholism U10 AA008401 (National Institute on Alcohol Abuse and Alcoholism).