Genetic Liability to Cannabis Use Disorder and COVID-19 Hospitalization

Abstract

Behavioral and life style factors plausibly play a role in likelihood of being hospitalized for COVID-19. Genetic vulnerability to hospitalization after SARS-CoV2 infection may partially relate to comorbid behavioral risk factors, especially the use of combustible psychoactive substances. Paralleling the COVID-19 crisis has 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. By leveraging genome-wide association summary statistics of CUD and COVID-19, we find that at least 1/3 ^rd of the genetic vulnerability to COVID-19 overlaps with genomic liability to CUD (rg=.34, p=0.0003). Genetic causality as a potential mechanism of risk could not be excluded. The association between CUD and COVID-19 remained when accounting for genetics of trying marijuana, tobacco smoking (ever smoking regularly, cigarettes per day, smoking cessation, age of smoking initiation), BMI, fasting glucose, forced expiration volume, education attainment, and Townsend deprivation index. Heavy problematic cannabis use may increase chances of hospitalization due to COVID-19 respiratory complications. Curbing excessive cannabis use may be an essential strategy in COVID-19 mitigation.

Figure 1.. Genetic associations between Substance Use Phenotypes and COVID-19 Hospitalization

A) Genetic correlations between COVID-19 hospitalization and inhalation substance use phenotypes. Cannabis Use Disorder (CUD) is highlighted in green. CPD = Cigarettes per day, Age Smoke = Age of first becoming a regular smoker, Ever Smoke = Ever being a regular smoker, Cannabis Use = Any lifetime cannabis use. (B) Heat map of genetic correlations between all phenotypes included in the study. COVID-19 Hosp = COVID-19 hospitalization (Variable COVIDB2 from the COVID Host Genomics Consortium(4)). TDI = Townsend Deprivation Index, COVID-19 Hosp. = COVID-19 hospitalization, Edu Attain = Education attainment, BMI = Body Mass Index. FEV1 = Forced Expiration Volume for 1 second, Fast Gluc = Fasting Glucose.