Genetic analyses point to alterations in immune-related pathways underpinning the association between psychiatric disorders and COVID-19

Abstract Current literature suggests that people with psychiatric disorders have higher risk of SARS-CoV-2 infection and a worse prognosis of the disease. We aimed to study the genetic contribution to these associations in a range of psychiatric disorders and COVID-19, and determine whether these are unique or shared across psychiatric disorders. Using the largest available genome-wide association studies, we analysed the genetic overlap between six psychiatric disorders and COVID-19. We further identified specific regions of the genome that are shared across the psychiatric disorders and COVID-19 using pairwise GWAS, and examined which genes are present in these regions. Finally, we sought evidence for causal associations using Mendelian Randomization methods. We found a significant genetic overlap between depression and ADHD, with both COVID-19 susceptibility and severity, as well as between anxiety and COVID-19 severity. We identified specific regions of the genome shared between several psychiatric disorders and COVID-19. However, no region was common across all psychiatric disorders and COVID-19. Gene-based analysis in these genomic regions suggested possible links with immune-related pathways such as thyroid homeostasis, inflammation and stress response. Finally, we provide evidence of a potential causal relationship between ADHD and higher COVID-19 susceptibility and severity, and between depression and higher susceptibility to COVID-19. Our results support the hypothesis that the relationship between psychiatric disorders and COVID-19 risk is likely due to shared alterations in immune-related pathways and are not as a result of environmental factors alone, shedding light on potentially viable therapeutic targets.