Genetic predispositions to psychiatric disorders and the risk of COVID-19

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.

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

“…(6, 7) Some studies have reported common alterations in biological pathways for psychiatric disorders and COVID-19, (8) which suggests a potential role for shared common genetic risk factors between both conditions. In line with these observations, a genetic predisposition to psychiatric disorders has been associated with COVID-19 susceptibility and severity, (9) and recent studies have reported signi cant genetic correlations between depression and COVID-19. (10) Despite shared genetic overlap, studies using genetic data have failed to nd evidence of causal associations between selected psychiatric disorders and COVID-19 in support of the results obtained in observational studies.…”

Trends in incident diagnoses and drug prescriptions for anxiety and depression during the COVID-19 pandemic: an 18-month follow-up study based on the UK Biobank

“…Alternatively, individuals who had taken a COVID-19 test might also have temporarily reduced social contact, i.e., being quarantined or isolated, to avoid infecting others, resulting in negative impact on mental health [38]. On the other hand, studies conducted by our [39,40] and other research groups [41] demonstrated a bidirectional association between COVID-19 and psychiatric disorders, suggesting that individuals with propensity for psychiatric disorders may be more vulnerable for COVID-19 infection and adverse outcomes. With respect to the test result, we observed a similar increased risk of anxiety and depression for individuals with both negative and positive results, which is in agreement with Abel et al's finding [12].…”

The genetic landscape of substance use disorders

“…created a latent general addiction risk factor and found that the PGS based on this factor were associated with substance use disorders, psychopathologies, somatic conditions, and environments associated with the onset of addictions. In another study, a PGS based on substance misuse was significantly predictive of COVID-19 [80].…”