GWAS of Cannabis Abuse

Researchers from iPSYCH in Denmark have identified a gene that appears to be associated with the abuse of cannabis. Demontis et al. (2019) report that variant rs56372821 is a strong expression quantitative trait locus (eQTL) for cholinergic receptor nicotinic α2 subunit (CHRNA2).  This gene appears to influence the number of nicotine receptors in the brain. The authors show here that the number of these receptors correlates to cannabis use disorder (CUD).

This Genome Wide Association Study (GWAS) study used a case cohort of over 2,000 cannabis abusers and compared to 50,000 control subjects and then repeated using a case cohort of 5,5000 cannabis abusers and over 300,000 control subjects.   Each time, they found an association of CHRNA2 expression with CUD and using polygenic risk scores a decrease of CUD is associated with an increased load of the variant.   

Unfortunately, the primary research is behind the paywall.  The summary statistics and results are apparently available for download at the iPSYCH website (  Download requires completing an application form and membership into the PGC.  So, not really publicly available.  

However, still the findings have been replicated in different cohorts and are not entirely novel, these results build on other work in the primary literature.  There are more than a few studies showing this variant and expression of this nicotinic receptor associated with not only CUD, but also with other psychiatric disorders like major depression and schizophrenia.  Solidly great work to build upon the idea that substance abuse and psychiatric diseases can and do have a genetic component. This really opens up treatment possibilities for rational drug and therapy design. YIPEE!

Anyhow, the Psychiatric Genomics Consortium (PGC) and the iPSYCH referenced in these papers are great collaborations and appear to be well organized data warehouses to offer genomic data for the study of psychiatric disease. These are worth more investigating for those interested.  

Free Resources for the Analysis of Data Pt. I