Abstract
BACKGROUND: Whether a genetic predisposition to psychiatric disorders is associated with coronavirus disease 2019 (COVID-19) is unknown. METHODS: Our analytic sample consisted of 287,123 white British participants in UK Biobank who were alive on 31 January 2020. We performed a genome-wide association study (GWAS) analysis for each psychiatric disorder (substance misuse, depression, anxiety, psychotic disorder, and stress-related disorders) in a randomly selected half of the study population ("base dataset"). For the other half ("target dataset"), the polygenic risk score (PRS) was calculated as a proxy of individuals' genetic predisposition to a given psychiatric phenotype using discovered genetic variants from the base dataset. Ascertainment of COVID-19 was based on the Public Health England dataset, inpatient hospital data, or death registers in UK Biobank. COVID-19 cases from hospitalization records or death records were considered "severe cases." The association between the PRS for psychiatric disorders and COVID-19 risk was examined using logistic regression. We also repeated PRS analyses based on publicly available GWAS summary statistics. RESULTS: A total of 143,562 participants (including 10,868 COVID-19 cases) were used for PRS analyses. A higher genetic predisposition to psychiatric disorders was associated with an increased risk of any COVID-19 and severe COVID-19. The adjusted odds ratio (OR) for any COVID-19 was 1.07 (95% confidence interval [CI] 1.02-1.13) and 1.06 (95% CI 1.01-1.11) among individuals with a high genetic risk (above the upper tertile of the PRS) for substance misuse and depression, respectively, compared with individuals with a low genetic risk (below the lower tertile). Slightly higher ORs were noted for severe COVID-19, and similar result patterns were obtained in analyses based on publicly available GWAS summary statistics. CONCLUSIONS: Our findings suggest a potential role of genetic factors in the observed phenotypic association between psychiatric disorders and COVID-19. Our data underscore the need for increased medical surveillance for this vulnerable population during the COVID-19 pandemic.