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

  1. Wenwen Chen
  2. Yu Zeng
  3. Chen Suo
  4. Huazhen Yang
  5. Yilong Chen
  6. Can Hou
  7. Yao Hu
  8. Zhiye Ying
  9. Yajing Sun
  10. Yuanyuan Qu
  11. Donghao Lu
  12. Fang Fang
  13. Unnur A. Valdimarsdóttir
  14. Huan Song

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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.

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  1. Version published to 10.1186/s12916-022-02520-z
  2. ScreenIT

    SciScore for 10.1101/2021.02.23.21251866: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    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:
    Our study has several limitations. First, the genetic profile of stress-related disorders was not established due to limited sample size. We could therefore not examine the genetic association between stress-related disorders and COVID-19. Second, in selecting SNPs for PRS construction, relatively loose p-value thresholds were applied. For example, as determined by the presence of highest R square, the threshold was 0.5, 0.1 and 0.2 for substance misuse, depression, and anxiety, respectively, possibly resulting in noise from redundant loci and subsequently unclear impact on the studied association. Third, the UK Biobank participants are not representative of the general population in the UK38 and our genetic analysis is further limited to participants with white European ancestry which reduces the generalization of our findings to the whole UK population and other populations. Last, given that the PRS contains information from relatively common variants only, the impact of rare and low frequency genetic variants needs further investigation. In conclusion, in the UK Biobank population, we found genetic predisposition to psychiatric disorders to be associated with increased risk of COVID-19, which may partially explain the observed phenotypic association between psychiatric disorders and COVID-19. Notably, the gene-driven susceptibility to COVID-19 among individuals prone to psychiatric disorders underscores the need of extra awareness and medical care for this vulnerable popul...

    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.
    • No protocol registration statement was detected.

    About SciScore

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  3. Version published to 10.1101/2021.02.23.21251866v1 on medRxiv