Genome-wide cross-trait analysis and Mendelian randomization reveal a shared genetic etiology and causality between COVID-19 and venous thromboembolism

Abstract

Venous thromboembolism occurs in up to one-third of patients with COVID-19. Venous thromboembolism and COVID-19 may share a common genetic architecture, which has not been clarified. To fill this gap, we leverage summary-level genetic data from the latest COVID‐19 host genetics consortium and UK Biobank and examine the shared genetic etiology and causal relationship between COVID-19 and venous thromboembolism. The cross-trait and co-localization analyses identify 2, 3, and 4 shared loci between venous thromboembolism and severe COVID-19, COVID-19 hospitalization, SARS-CoV-2 infection respectively, which are mapped to ABO, ADAMTS13, FUT2 genes involved in coagulation functions. Enrichment analysis supports shared biological processes between COVID-19 and venous thromboembolism related to coagulation and immunity. Bi-directional Mendelian randomization suggests that venous thromboembolism was associated with higher risk of three COVID-19 traits, and SARS-CoV-2 infection was associated with a higher risk of venous thromboembolism. Our study provides timely evidence for the genetic etiology between COVID-19 and venous thromboembolism (VTE). Our findings contribute to the understanding of COVID-19 and VTE etiology and provide insights into the prevention and comorbidity management of COVID-19.

Causal Association Between Peripheral blood immune cells and Rheumatoid Arthritis: A Bidirectional Mendelian Randomization Study

“…A 'leave one out' analysis was conducted to assess the in uence of individual SNPs on the exposure-outcome relationship, with a p-value over 0.05 signifying no horizontal pleiotropy [29] . To clarify whether the immune cell traits and RA genetically share the same genetic variant, we performed gene colocalization analysis [30] . To mitigate false positives in multiple testing, false discovery rate (FDR) correction was applied.…”

Venous thromboembolism and severe COVID-19: a Mendelian randomization trial and transcriptomic analysis

“…Hence, immunothrombosis plays a central pathogenic role in sCOVID-19 connecting it to respiratory failure and systemic hypercoagulability. Prior cross-trait meta- and colocalization analyses indicated that certain known VTE-associated genes (e.g., ABO, FUT2 , and ADAMST13 , et al) were strongly associated with COVID-19 diseases severity ( 19 , 20 ). An MR investigation involving 12 coagulation factors and COVID-19 severity reported that VWF is strongly correlated with COVID-19 susceptibility and hospitalization ( 19 ).…”

“…An MR investigation involving 12 coagulation factors and COVID-19 severity reported that VWF is strongly correlated with COVID-19 susceptibility and hospitalization ( 19 ). Huang and colleagues performed an MR analysis to genetically predict that VTE is intricately linked to enhanced COVID-19 infection and hospitalization risks ( 20 ). This report further validated the direct correlation between genetically estimated VTE and enhanced sCOVID-19 with respiratory failure risk.…”