Abstract
Objective
This study aimed to evaluate the host genetic liability of covid-19 with platelet traits using the Mendelian Randomization (MR) approach.
Method
We conducted a bi-directional two-sample MR using summary statistics from the largest genome-wide association study (GWAS) of three covid-19 severity (SARS-CoV-2 infection, covid-19 hospitalization and severe covid, N~1,059,456 to 1,557,411) and four platelet traits (mean platelet volume [MPV], plateletcrit, platelet distribution width, and platelet count; N=408,112). Inverse variance weighted (IVW), median weighted, MR-Egger, and contamination mixture methods were used to estimate the causal association.
Result
Null and inconsistent association in the IVW and sensitivity analyses were observed for SARS-CoV-2 infection and covid-19 hospitalization with platelet traits. For severe covid-19, significant associations with MPV and platelet count were observed in the IVW and sensitivity analyses, w ith the betaIVW of 0.01 (95% CI: 0.005 to 0.016, p-value=3.51x10-4) and -0.009 (95% CI: -0.015 to -0.002, p-value=0.008) per doubling in odds of severe covid-19, respectively. Conversely, null associations were observed for platelet traits with covid-19 traits.
Conclusion
Host genetic liability to severe covid-19 was causally associated with increased MPV and reduced platelet count, which may provide insight in evaluating hypercoagulability and thromboembolic events in covid-19 patients.
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