Genetics and Substance Addiction

by Elizabeth Da Theresa

Credits: Natasha Shabasheva

The genetics of an individual, form one of the many relevant factors involved in the development of an addiction. Whilst peer, familial and environmental factors greatly influence accessibility and attitude towards addictive substances, genetics are proven to be a significant point of vulnerability. Substance abuse results in neuroadaptive changes (withdrawal, cravings and tolerance) and diagnosis of an addiction is often made after neuroadaptive changes have occurred which lead to the addict displaying uncontrolled substance abuse.

Genes relevant to an individual’s vulnerability to addiction are monoamine moderators (such as serotonin, norepinephrine and dopamine) as they affect an individual’s response to an addictive substance. Examples are the COMT gene that is significant in regulating levels of dopamine in the prefrontal cortex of the brain and the serotonin transporter (SLC6A4) that regulates serotonin in the synapses; both greatly impact vulnerability to addiction by affecting how an individual may feel in response to taking a substance.

However, it is difficult to pinpoint ‘risk alleles’ due to genetic complexities involving the expression of phenotypes not coded for by alleles of the individual but expressed due to environmental factors as well as heterogeneity and polygenicity that introduce phenotypic variance. However analysis of genomes in genome-wide association studies for alleles that reoccur among groups with the same conditions, can be used to identify specific alleles associated with certain addictions. Genome-wide association studies require large groups and diverse samples with particular interest in extreme phenotypes, unfortunately this data is not always easily attained. Heterogeneity and polygenicity (when a phenotype is influenced by multiple genes or gene mutations) can be investigated in monozygotic and dizygotic twin studies as when multiple genes in combination are required the monozygotic: dizygotic ratio is higher.

Overall genetics attribute a significant influence, with heritability varying between substances but further research is vital. The rehabilitation and treatment of individuals suffering with addiction puts great economic stress on the healthcare industry, but a better understanding of genetic vulnerabilities could help assess an individual’s vulnerability to developing an addiction, individualise prevention and treatment and identify new therapeutic targets.

Citations

NIDA. 2023, March 22. New NIH study reveals shared genetic markers underlying substance use disorders. Retrieved from https://nida.nih.gov/news-events/news-releases/2023/03/new-nih-study-reveals-shared-genetic-markers-underlying-substance-use-disorders on 2024, February 21

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Ducci F, Goldman D. The genetic basis of addictive disorders. Psychiatr Clin North Am. 2012 Jun;35(2):495-519. doi: 10.1016/j.psc.2012.03.010. PMID: 22640768; PMCID: PMC3506170.