LAUSR

This study aimed to evaluate the host genetic liability of coronavirus disease 2019 (covid‐19) with platelet traits using the Mendelian randomization (MR) approach. We conducted a bidirectional two‐sample MR using summary statistics from the largest genome‐wide association study of three variables, covid‐19 severity (severe acute respiratory syndrome coronavirus 2 [SARS‐CoV‐2] infection, covid‐19 hospitalization, and severe covid‐19, N = ~1 059 456–1 557 411) 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. Null and inconsistent associations 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, with the betaIVW of 0.01 (95% confidence interval [CI]: 0.005–0.016, p = 3.51 × 10−4) and −0.009 (95% CI: −0.015 to −0.002, p = 0.008) per doubling in odds of severe covid‐19, respectively. Conversely, null associations were observed for platelet traits with covid‐19 traits. In conclusion, host genetic liability to severe covid‐19 was causally associated with increased MPV and reduced platelet count, which may provide insights into evaluating hypercoagulability and thromboembolic events in covid‐19 patients.