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[Preprint]. 2022 Feb 28:2022.02.28.22271562.
doi: 10.1101/2022.02.28.22271562.

Genetic Examination of Hematological Parameters in SARS-CoV-2 Infection and COVID-19

Bryce Rowland  1 , Quan Sun  1 , Wanjiang Wang  1 , Tyne Miller-Fleming  2 , Nancy Cox  2 , Misa Graff  3 , Annika Faucon  2 , Megan M Shuey  4 , Elizabeth E Blue  5 , Paul Auer  6 , Yun Li  1   7   8 , Vijay G Sankaran  9 , Alexander P Reiner  10 , Laura M Raffield  7
Affiliations

Genetic Examination of Hematological Parameters in SARS-CoV-2 Infection and COVID-19

Bryce Rowland et al. medRxiv. .

Update in

Abstract

Background: People hospitalized with COVID-19 often exhibit hematological alterations, such as lower lymphocyte and platelet counts, which have been reported to associate with disease prognosis. It is unclear whether inter-individual variability in baseline hematological parameters prior to acute infection influences risk of SARS-CoV-2 infection and progression to severe COVID-19.

Methods: We assessed the association of blood cell counts and indices with incident SARS-CoV-2 infection and severe COVID-19 in UK Biobank and the Vanderbilt University Medical Center Synthetic Derivative (VUMC SD). Since genetically determined blood cell measures better represent cell abundance across the lifecourse, we used summary statistics from genome-wide association studies to assess the shared genetic architecture of baseline blood cell counts and indices on COVID-19 outcomes.

Results: We observed inconsistent associations between measured blood cell indices and both SARS-CoV-2 infection and COVID-19 hospitalization in UK Biobank and VUMC SD. In Mendelian randomization analyses using genetic summary statistics, no putative causal relationships were identified between COVID-19 related outcomes and hematological indices after adjusting for multiple testing. We observed overlapping genetic association signals between hematological parameters and COVID-19 traits. For example, we observed overlap between infection susceptibility-associated variants at PPP1R15A and red blood cell parameters, and between disease severity-associated variants at TYK2 and lymphocyte and platelet phenotypes.

Conclusions: We did not find convincing evidence of a relationship between baseline hematological parameters and susceptibility to SARS-CoV-2 infection or COVID-19 severity, though this relationship should be re-examined as larger and better-powered genetic analyses of SARS-CoV-2 infection and severe COVID-19 become available.

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Conflict of interest statement

Conflict of Interest Statement

The authors declare that they have no competing interests.

Figures

Figure 1.
Figure 1.. Coincident loci analysis results for rs4801778 and high light scatter reticulocyte proportion in UKB GWAS.
rs4801778 (diamond), a lead variant in the HGI COVID-19 GWAS for SARS-CoV-2 infection, was found to be a coincident signal with rs11541192, a distinct variant for high light scatter reticulocyte proportion (HLSR%). rs11541192 is a missense variant for PPP1R15A. Triangles are conditionally independent GWAS variants for blood cell traits as determined by conditional analysis in Vuckovic et al. 2020 [23]. Legend: r2 = r2.
Figure 2.
Figure 2.. Coincident loci analysis results for rs74956615 and lymphocyte and platelet count in UKB GWAS.
rs74956615 (diamond), a lead variant in the HGI COVID-19 GWAS for COVID-19 severe illness and hospitalization, was found to be a coincident signal with rs34536443, a distinct variant for platelet and lymphocyte traits. rs34536443 is a missense variant for TYK2. Triangles are conditionally independent GWAS variants for blood cell traits as determined by conditional analysis in Vuckovic et al. 2020. Legend: r2 = r2.
Figure 3.
Figure 3.. Coincident loci analysis results for rs35081325 and monocyte count in UKB GWAS.
rs35081325 (diamond), a lead variant in the HGI COVID-19 GWAS for COVID-19 severe illness and hospitalization was not found to be coincident with any of the nine nearby monocyte GWAS distinct variants. Triangles are conditionally independent GWAS variants as determined by conditional analysis in Vuckovic et al. 2020. Legend: r2= r2.
Figure 4.
Figure 4.. Coincident loci analysis results for rs35081325 and eosinophil percentage in UKB GWAS.
rs35081325 (diamond), a lead variant in the HGI COVID-19 GWAS for COVID-19 severe illness and hospitalization was found to be coincident with rs74586549, a distinct GWAS variant for eosinophil proportion. Legend: r2 = r2.
Figure 5.
Figure 5.. Selected Mendelian randomization results.
Each subfigure shows the estimates (denoted by dots) and their 95% confidence intervals (denoted by the range of each bar) for four different estimands. Blue color represents significant associations.
See this image and copyright information in PMC

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