Unraveling COVID-19 relationship with anxiety disorders and symptoms using genome-wide data

There is still a limited understanding of the dynamics contributing to the comorbidity of COVID-19 and anxiety outcomes. To dissect the pleiotropic mechanisms contributing to COVID-19/anxiety comorbidity, we used genome-wide data from UK Biobank (up to 420,531 participants), FinnGen Project (up to 329,077 participants), Million Veteran Program (175,163 participants), and COVID-19 Host Genetics Initiative (up to 122,616 cases and 2,475,240 controls). Specifically, we assessed global and local genetic correlation and genetically inferred effects linking COVID-19 outcomes (infection, hospitalization, and severe respiratory symptoms) to anxiety disorders and symptoms. We observed a strong genetic correlation of anxiety disorder with COVID-19 positive status (rg = 0.35, p = 2×10−4) and COVID-19 hospitalization (rg = 0.31, p = 7.2×10−4). Among anxiety symptoms, “Tense, sore, or aching muscles during worst period of anxiety” was genetically correlated with COVID-19 positive status (rg = 0.33, p = 0.001), while “Frequent trouble falling or staying asleep during worst period of anxiety” was genetically correlated with COVID-19 hospitalization (rg = 0.24, p = 0.004). Through a latent causal variable analysis, we observed that COVID-19 outcomes have statistically significant genetic causality proportion (gcp) on anxiety symptoms (e.g., COVID-19 positive status→“Recent easy annoyance or irritability” │gcp│ = 0.18, p = 6.72×10−17). Conversely, anxiety disorders appear to have a possible causal effect on COVID-19 (│gcp│ = 0.38, p = 3.17×10−9). Additionally, we also identified multiple loci with evidence of local genetic correlation between anxiety and COVID-19. These appear to be related to genetic effects shared with lung function, brain morphology, alcohol and tobacco use, and hematologic parameters. This study provided insights into the pleiotropic mechanisms linking COVID-19 and anxiety outcomes, suggesting differences between dynamics related to anxiety disorders and those related to anxiety symptoms. •COVID-19 has been associated with increased anxiety symptoms.•Individuals with anxiety disorders have a higher risk of severe COVID-19 outcomes.•Possible causal relationships link COVID-19 and anxiety.•Specific genomic regions could contribute to COVID-19 association with anxiety.