Genetic correlations between alcohol use disorder (AUD), cannabis use disorder (CUD), opioid use disorder (OUD), tobacco use disorder (TUD) and a range of complex traits. Genetic correlations extracted from recent studies that applied linkage disequilibrium score regression (refs. 9, 18, 25, 26, 43, 138). Genetic variations and family members’ behaviors can create an environment where substance abuse is more likely to occur, especially if early life experiences involve trauma, neglect, or substance use modeling. Scientists will be able to translate this knowledge into new treatments directed at specific targets in the Drug rehabilitation brain or to treatment approaches—called pharmacogenomics.
- However, rather than blindly charging ahead with expensive gene identification efforts, our field would benefit from more thoughtful discussion about what strategies to pursue—both genetic and environmental—to have the greatest impact on reducing substance use problems.
- No, while genetics play a role, substance abuse is influenced by a combination of genetic, environmental, and behavioral factors.
Opioid painkillers
The paper in this issue by de Leon and Diaz (2012) discusses how comorbid conditions can be harnessed to investigate the genetics of SUD (in this case the comorbidity of schizophrenia or mood disorders with nicotine addiction). Although nicotine addiction and schizophrenia demonstrate the highest comorbidity rates, other diseases, and particularly mood disorders, also exhibit very high prevalence rates of smoking. They also discuss the potential causality role that early exposure to nicotine may have in increasing the risk of depression. The findings in one study showed that environmental factors explained more of the risk for opioid dependence than polygenic risk scores—a number estimating how genetic variants affect is addiction genetic an individual’s risk of developing a disease.
How do genetics affect an individual’s vulnerability to substance abuse?
So far, these researchers have identified 47 genetic variants linked to substance disorders, including 32 for tobacco, 9 for alcohol, 5 for cannabis, and one for opioid addiction. In this post, I provide an overview of key research on the genetic inheritance of substance use disorders such as alcohol use disorder, opioid use disorder, and cannabis/marijuana use disorder. There are several approved and effective pharmacological treatments of substance use disorders 117. Incorporating genetic information into the treatment decision-making process may potentially improve patient management and outcomes 118. Here, we will summarize the results of pharmacogenomics studies investigating how genes affect a person’s responses to pharmacological treatment, with a specific focus on alcohol, tobacco and opioid use disorders. Consistent with high rates of comorbidity, there is substantial overlap in genetic risk factors between different substance use disorders.
Tobacco use disorder
- If you use drugs when you’re an adolescent, you are more likely to develop lifetime addiction.
- GWAS and sequencing are extremely powerful tools because they can find a connection between a known gene or genes and a disorder, and can identify genes that may have been overlooked or were previously unknown.
- Genetic variants that modify the expression of a gene by acting upon the regulatory elements of the gene.
Recent studies have observed substantial pleiotropy at genome-wide 45, regional 46, and transcriptomic 47 levels. Genetic correlations range from ~0.45 (TUD and OUD) to ~0.70 (AUD and OUD) (see Fig. 2a) suggesting that while there is extensive overlap, there are also substance-specific genetic effects. In this study, maltreated boys carrying the MAOA low-activity genotype were more likely to develop antisocial problems than boys with the high-activity genotype.
Family Systems Theory
- Genetics can open the door, but environment often determines whether someone walks through it.
- For example, in hypothesis-driven studies, genes in different brain regions were selectively expressed, downregulated, or knocked out in animal models of addiction 3.
- Wang et al.15 examined the effects of consuming different classes of drugs, such as anesthetics, psychotropics, and mixed consumption, on the balance and reaction times of abstinent women.
- Genetics alone cannot determine whether someone will develop a substance abuse disorder.
- Research has shown that certain genetic variations can increase a person’s susceptibility to addiction.
Genetic effect estimates from genome-wide association studies can be used to calculate PGS that provide an indication of an individual’s genetic liability to a certain trait or disease. PGS can be calculated by multiplying the number of risk alleles a person carries with the SNP effect sizes from a GWAS of that phenotype and aggregating across all SNPs (taking LD into account). In research, these scores can then be used to validate the predictive power of the GWAS results, estimate associations with other traits, or test gene-environment interplay. Interesting, divergent patterns of association are also observed within different aspects of consumption (e.g., quantity vs. frequency).