Pot Luck?

A new National Institute of Health (NIH) study appears to have identified genetic markers that underlie substance use disorders (1). Potentially big news given that, in the US alone, more than 46.3 million people aged 12 or older had at least one substance use disorder, and only 6.3 percent of these had received treatment, according to the 2021 National Survey on Drug Use and Health (2). Evidently, addiction represents a growing public health crisis. 

Recent large-scale genome-wide association studies – which examine entire genomes for regions of genetic variation associated with the same disorder, condition, or behavior among multiple people – have previously identified loci associated with specific substance use disorders. However, there is very limited knowledge of the molecular genetic underpinnings of addiction in general. 

Now, in a sample of over one million participants with both African and European ancestry, the NIH researchers used multivariate genome-wide association meta-analysis to pinpoint areas in the genome associated with general addiction risk – as well as the risk of specific substance use disorders like alcohol, nicotine, cannabis, and opioid use disorders. Results revealed 19 independent single-nucleotide polymorphisms (SNPs) that are significantly associated with general addiction risk and 47 SNPs for specific substance disorders among the European ancestry sample. Analysis of the African ancestry sample revealed one SNP associated with general addiction risk and one substance-specific SNP for risk of alcohol use disorder. The authors noted that their analysis of individuals of African ancestry had few discoveries and highlighted the need for systematic data collection in globally representative populations.

Across ancestries, PDE4B was significant (among other genes), suggesting dopamine regulation as a cross-substance vulnerability. These findings could lead to more effective prevention and treatment targets for multiple substance use disorders.