The genetics of substance dependence.
paper
Primary
Public
- Authors
- Wang, Jen-Chyong; Kapoor, Manav; Goate, Alison M
- Year
- 2012
- Journal
- Annual review of genomics and human genetics
- PMID
- 22703173
- DOI
- 10.1146/annurev-genom-090711-163844
- PMCID
- PMC3474605
A large segment of the population suffers from addiction to alcohol, smoking, or illicit drugs. Not only do substance abuse and addiction pose a threat to health, but the consequences of addiction also impose a social and economic burden on families, communities, and nations. Genome-wide linkage and association studies have been used for addiction research with varying degrees of success. The most well-established genetic factors associated with alcohol dependence are in the genes encoding alcohol dehydrogenase (ADH), which oxidizes alcohol to acetaldehyde, and aldehyde dehydrogenase (ALDH2), which oxidizes acetaldehyde to acetate. Recently emerging genetic studies have linked variants in the genes encoding the Ξ±3, Ξ±5, and Ξ²4 nicotinic acetylcholine receptor subunits to smoking risk. However, the influence of these well-established genetic variants accounts for only a small portion of the heritability of alcohol and nicotine addiction, and it is likely that there are both common and rare risk variants yet to be identified. Newly developed DNA sequencing technologies could potentially advance the detection of rare variants with a larger impact on addiction risk.
Interaction of genetic and environmental factors in the development of substance dependence. The initiation of substance use is influenced largely by environmental factors; the use of the addictive substance is affected largely by genetic factors.
The role of ADH and ALDH2 variants in the alcohol metabolic pathway.
Three distinct loci across the CHRNA5-CHRNA3-CHRNB4 gene cluster on human chromosome 15. Triangles represent single nucleotide polymorphisms (SNPs). SNP position is not drawn to scale.
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