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

  1. Yong Xiang
  2. Jinghong Qiu
  3. Ruoyu Zhang
  4. Carlos Kwan-Long Chau
  5. Shitao Rao
  6. Hon-Cheong So

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

Background

More than 180 million cases of COVID-19 have been reported worldwide. It has been proposed that neuropsychiatric 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 GWAS summary statistics from the COVID-19 Host Genetics Initiative. A variety of MR methods including those accounting for horizontal pleiotropy were employed.

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 causal associations. We observed 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.

Article activity feed

  1. Version published to 10.1101/2021.06.29.21259609v2 on medRxiv
  2. ScreenIT

    SciScore for 10.1101/2021.06.29.21259609: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    RandomizationMendelian randomization analysis: Here we performed two-sample MR, in which the instrument-exposure and instrument-outcome associations were estimated in different samples.
    Blindingnot detected.
    Power AnalysisThe statistical power is however weaker.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    One important limitation of observational studies is the risk of residual confounding. For example, socioeconomic status is not controlled for by Tanquet et al., and incomplete data on some covariates may lead to inadequate control for confounders. In addition, the above studies typically focused on a few psychiatric disorders, and the coverage is not as comprehensive as the current study. In this MR study, liability to AD, ADHD, ALD, OD, PTSD and SA were associated with increased risk and/or severity of COVID-19 infection/severity. As discussed above, there was evidence that ADHD1 and substance use disorders46 may be associated with heightened risk of COVID-19. There were no previous studies that directly addressed association of PTSD and history of suicide with susceptibility to infection. However, in Yang et al46, stress-related disorders were associated with higher risks of infection, hospitalization and mortality, although the results were non-significant. Suicide attempts (SA) is linked to many psychiatric disorders (e.g. mood, anxiety and psychotic disorders) and previous studies have shown that prior psychiatric disorders as a whole were associated with COVID-19. There have been relatively few studies on the associations of psychiatric disorders with risks/severity of pneumonia. A study using linked hospital records showed that the risk of pneumococcal disease was elevated for patients with SCZ, BD, anxiety or depression8. We found potential causal relationships of an...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a protocol registration statement.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.06.29.21259609v1 on medRxiv