A recent study has identified multiple loci associated with general addiction risk. The research, published this week in Nature Mental Health, could lead to the identification of drugs that could treat addiction for multiple substances, rather than for one specific substance use disorder.
Substance use disorders – more common than we think
Substance use disorders are among some of the most common ailments found in the adult population. Over 46 million individuals in the US are thought to have an addiction to one or more dangerous substances. Drug and alcohol consumption is a major risk factor for premature death and comes with significant socioeconomic strain. Furthermore, addiction to one substance often goes hand-in-hand with abuse of others, yet treatment for general substance abuse is scarce.
Propensity to addiction is somewhat heritable, with substance use disorders often seen to run in families. However, this familial association could be due to genetic or environmental risk factors, and as of yet the biological aspects are not fully understood. In the largest study of its kind, the researchers from Washington University in St. Louis carried out a meta-analysis of previous genome-wide association studies (GWAS), totalling over one million genomes, in a bid to find molecular mechanisms underpinning addiction.
One million genomes
Overall, the meta-analysis revealed that 19 genetic loci were associated with the risk of general addiction, whilst various others were linked to individual substances such as alcohol, opioids and cannabis (Figure 1). Among these significant genes were various regulators of dopamine signalling. Dopamine is already implicated in addiction, with the “happy hormone” released at elevated levels when someone takes an addictive substance. Eventually, an individual may require more and more of the substance to obtain the same feeling.
Figure 1: Manhattan plot showing results of the meta-analysis. 17 of the 19 significant polymorphisms are shown here, situated above the dotted line representing genome-wide significance. Taken from Hatoum et al., 2023.
To test whether the genes were predictive for future addiction risk, the team analysed the genomes of young children. Those with close relatives suffering from addiction were more likely to harbour the relevant risk loci and exhibit impulsive behaviours. The risk loci were also associated with other physical and mental health disorders. This further validated a known link between substance abuse and psychiatric illnesses.
Where next?
Substance abuse can have considerable effects on not only the individual but also their families, friends and the wider community. There is also a significant public health burden associated with drug use. Currently, medications exist that can target addiction to specific substances, but none that combat substance use more generally. To combat this, the team assessed whether any approved pharmaceutical drugs could be used to target the loci identified in this study, with a view to identify therapies that could be used to treat general substance abuse.
Discussing how the results could help treat those suffering from addiction, co-senior author Arpana Argawal stated: “This study represents a major advance in understanding how genetic factors predispose people to substance use disorders. While we have known for a while that many genetic factors are shared between different substance use disorders, our study identified some of the contributing genes, providing avenues for future biological and therapeutic discoveries for individuals with multiple addictions.”
