Causal Associations Between Blood Lipids and COVID-19 Risk: A Two-Sample Mendelian Randomization Study

  1. Kun Zhang
  2. Shan-Shan Dong
  3. Yan Guo
  4. Shi-Hao Tang
  5. Hao Wu
  6. Shi Yao
  7. Peng-Fei Wang
  8. Kun Zhang
  9. Han-Zhong Xue
  10. Wei Huang
  11. Jian Ding
  12. Tie-Lin Yang

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Abstract

Coronavirus disease 2019 (COVID-19) is a global pandemic caused by the severe acute respiratory syndrome coronavirus 2. It has been reported that dyslipidemia is correlated with COVID-19, and blood lipids levels, including total cholesterol, HDL-C (high-density lipoprotein cholesterol), and LDL-C (low-density lipoprotein cholesterol) levels, were significantly associated with disease severity. However, the causalities of blood lipids on COVID-19 are not clear.

Approach and Results:

We performed 2-sample Mendelian randomization (MR) analyses to explore the causal effects of blood lipids on COVID-19 susceptibility and severity. Using the outcome data from the UK Biobank (1221 cases and 4117 controls), we observed potential positive causal effects of dyslipidemia (odds ratio [OR], 1.27 [95% CI, 1.08–1.49], P =3.18×10 −3 ), total cholesterol (OR, 1.19 [95% CI, 1.07–1.32], P =8.54×10 −4 ), and ApoB (apolipoprotein B; OR, 1.18 [95% CI, 1.07–1.29], P =1.01×10 −3 ) on COVID-19 susceptibility after Bonferroni correction. In addition, the effects of total cholesterol (OR, 1.01 [95% CI, 1.00–1.02], P =2.29×10 −2 ) and ApoB (OR, 1.01 [95% CI, 1.00–1.02], P =2.22×10 −2 ) on COVID-19 susceptibility were also identified using outcome data from the host genetics initiative (14 134 cases and 1 284 876 controls).

Conclusions:

In conclusion, we found that higher total cholesterol and ApoB levels might increase the risk of COVID-19 infection.

Graphic Abstract:

A graphic abstract is available for this article.

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  1. Version published to 10.1161/atvbaha.121.316324
  2. ScreenIT

    SciScore for 10.1101/2020.07.07.20147926: (What is this?)

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

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Instrumental variables (IVs) selection: We selected independent and genome-wide significant GWAS SNPs of HDL-c, LDL-c, TG, TC and dyslipidemia by use of the clumping algorithm in PLINK (http://pngu.mgh.harvard.edu/purcell/plink/) 13 at a suggestive threshold (r2 threshold = 0.001, window size = 1 Mb, p-value = 5 × 10−8).
    PLINK
    suggested: (PLINK, RRID:SCR_001757)
    The 1000 Genomes Project (http://www.internationalgenome.org/) data were used as the reference for linkage disequilibrium (LD) estimation.
    1000 Genomes Project
    suggested: (1000 Genomes Project and AWS, RRID:SCR_008801)
    In order to explore the association of TC and COVID-19, we implemented MAGMA to identify genes and gene sets in which multiple SNPs show moderate association to TC without reaching the stringent genome-wide significance level.
    MAGMA
    suggested: (MAGMA, RRID:SCR_005757)

    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:
    The limitations of the current study should be addressed. Due to the limitation of data resource, our findings are based on European cohort which cannot represent the universal conclusions for other ethnic groups. In addition, the potential mechanism of the risk effect for TC was discussed superficially, which needed to carry out further investigation to get more data support and further experimental verification. In summary, we carried out a two-sample MR design for blood lipids and COVID-19, and obtained following conclusions: 1) Dyslipidemia is causally associated with the susceptibility of COVID-19; 2) The higher total cholesterol level will increase the susceptibility of COVID-19; 3) The different susceptibility of COVID-19 in specific blood group may be partly explained by the TC concentration in diverse ABO blood groups; 4) The risk effect of total cholesterol on COVID-19 may be mediated by the dysfunction of immunity.

    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 10.1101/2020.07.07.20147926v1 on medRxiv