Shared genetic etiology and causality between COVID-19 and venous thromboembolism: evidence from genome-wide cross trait analysis and bi-directional Mendelian randomization study (preprint)

ABSTRACT

Venous thromboembolism (VTE) occurs in up to one third patients with COVID-19. VTE and COVID-19 may share a common genetic architecture in etiology, which has not been comprehensively investigated. In this study, we leveraged summary-level data from the latest COVID-19 host genetics consortium and UK Biobank to study the genetic commonality between COVID-19 traits and VTE. We found a positive genetic correlation between COVID-19 hospitalization and VTE (rg = 0.2320, P-value= 0.0092). The cross-trait analysis identified shared genetic loci between VTE and COVID-19 traits, including 8 for severe COVID-19, 11 for COVID-19 hospitalization, and 7 for SARS-CoV-2 infection. We identified seven novel mapped genes (LINC00970, TSPAN15, ADAMTS13, F5, DNAJB4, SLC39A8 and OBSCN) that were enriched for expression in the lung tissue, and in coagulation and immune related pathways. Eight genetic loci were found to share causal variants between COVID-19 and VTE, which are localized in the ABO, ADAMTS13 and FUT2 gene regions. Bi-directional Mendelian randomization analysis did not suggest a causal relationship between VTE and COVID-19 traits. Our study advances the understanding of shared genetic etiology of COVID-19 and VTE at the molecular and functional levels.