Neuropsychiatric disorders as risk factors and consequences of COVID-19: A Mendelian randomization study

Abstract

Background More than 170 million cases of COVID-19 have been reported worldwide. It has been proposed that psychiatric disorders may be risk factors and/or consequences of COVID-19 infection. However, observational studies could be affected by confounding bias. Methods We performed bi-directional two-sample Mendelian randomization (MR) analysis to evaluate causal relationships between liability to COVID-19 (and severe/critical infection) and a wide range of neuropsychiatric disorders or traits. We employed the latest GWAS summary statistics from the COVID-19 Host Genetics Initiative. A variety of MR methods including those accounting for horizontal pleiotropy were used. Results Overall we observed evidence that liability to COVID-19 or severe infection may be causally associated with higher risks of post-traumatic stress disorder (PTSD), bipolar disorder (BD) (especially BD II), schizophrenia (SCZ), attention deficit hyperactivity disorder (ADHD) and suicidal thought (ST) when compared to the general population. On the other hand, liability to a few psychiatric traits/disorders, for example ADHD, alcohol and opioid use disorders may be causally associated with higher risks of COVID-19 infection or severe disease. In genetic correlation analysis, cannabis use disorder, ADHD, and anxiety showed significant and positive genetic correlation with critical or hospitalized infection. All the above findings passed multiple testing correction at a false discovery rate (FDR)<0.05. For pneumonia, in general we observed a different pattern of associations, with bi-directional positive associations with depression- and anxiety-related phenotypes. Conclusions In summary, this study provides evidence for tentative bi-directional causal associations between liability to COVID-19 (and severe infection) and a number of neuropsychiatric disorders. Further replications and prospective studies are required to verify the findings.