Genetic Liability to Cannabis Use Disorder and COVID-19 Hospitalization

Hatoum, Alexander S.; Morrison, Claire L.; Colbert, Sarah M.C.; Winiger, Evan A.; Johnson, Emma C.; Agrawal, Arpana; Bogdan, Ryan

Background Vulnerability to COVID-19 hospitalization has been linked to behavioral risk factors, including combustible psychoactive substance use (e.g., tobacco smoking). Paralleling the COVID-19 crisis have been increasingly permissive laws for recreational cannabis use. Cannabis Use Disorder (CUD) is a psychiatric disorder that is heritable and genetically correlated with respiratory disease, independent of tobacco smoking. We examined the genetic relationship between CUD and COVID-19 hospitalization. Methods We estimated the genetic correlation between CUD (n case=14,080, n control=343,726) and COVID-19 hospitalization (n case=9,373, n control=1,197,256) using summary statistics from genome-wide association studies (GWASs). Using independent GWASs conducted prior to the pandemic, we controlled for several covariates (i.e., tobacco use phenotypes, problematic alcohol use, BMI, fasting glucose, forced expiration volume, education attainment, risk-taking, ADHD, and Townsend Deprivation Index; as well as chronic obstructive pulmonary disease, hypertension and type 2 diabetes) using genomic structural equation modeling. Genetic causality between CUD and COVID-19 hospitalization was estimated using latent causal variable models. Results Genetic vulnerability to COVID-19 was correlated with genetic liability to CUD (rG=0.423(.0965), p=1.33e-6); this association remained when accounting for genetic liability to related risk factors and covariates (b = 0.381 - 0.539, p=0.012 - 0.049). Latent causal variable analysis revealed causal effect estimates that were not statistically significant. Conclusions Problematic cannabis use and vulnerability to serious COVID-19 complications share genetic underpinnings that are unique from common correlates. While CUD may plausibly contribute to severe COVID-19 presentations, causal inference models yielded no evidence of putative causation. Curbing excessive cannabis use may mitigate COVID-19’s impact.