Genetic Liability to Cannabis Use Disorder and COVID-19 Hospitalization

Abstract

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 pandemic 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 (case: n = 14,080; control: n = 343,726) and COVID-19 hospitalization (case: n = 9373; control: n = 1,197,256) using summary statistics from genome-wide association studies. Using independent genome-wide association studies conducted before the pandemic, we controlled for several covariates (i.e., tobacco use phenotypes, problematic alcohol use, body mass index, fasting glucose, forced expiratory volume, education attainment, risk taking, attention-deficit/hyperactivity disorder, Townsend deprivation index, 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 (r _G = 0.423 [SE = 0.0965], p = 1.33 × 10^-6); this association remained when accounting for genetic liability to related risk factors and covariates (b = 0.381-0.539, p = .012-.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 the impact of COVID-19.

Keywords: COVID-19; Cannabis use disorder; Genetic correlations; Genome-wide association statistics; Tobacco use.

Figure 1

Genetic associations between substance use phenotypes and COVID-19 hospitalization. (A) Genetic correlations between COVID-19 hospitalization and substance use phenotypes. Cannabis use disorder (CUD) is highlighted in green. ∗Indicates nominally significant. ∗∗Indicates Bonferroni significant after accounting for all genetic correlations tested. Age of smoking initiation was reverse coded, such that younger age was more associated with other negative life outcomes and would be easier to interpret. (B) Heat map of genetic correlations between all phenotypes included in the study. COVID-19 hospitalization [Variable COVIDB2 from the COVID Host Genomics Initiative (4)]. ∗∗Indicates Bonferroni significant for all tests run (number of tests = 120). ADHD, attention-deficit/hyperactivity disorder; Age Smoke, age of smoking initiation; BMI, body mass index; Cannabis Use, any lifetime cannabis use; CPD, cigarettes/day; EA, education attainment; Ever Smoke, ever smoking tobacco; Fast Gluc, fasting glucose; FEV₁, forced expiratory volume for 1 second; PAU, problematic alcohol use; RT, risk taking; Smoking Cess, smoking cessation; TDI, Townsend deprivation index.