Exploration of the Causal Relationship and Mechanisms Between Serum Albumin and Venous Thrombosis: a Bidirectional Mendelian Randomization Analysis and Bioinformatics Study
Overview
Authors
Affiliations
Background: To explore the causal relationship between serum albumin and venous thromboembolism (VTE) comprises deep vein thrombosis (DVT) and its consequential condition, pulmonary embolism (PE), through Mendelian randomization (MR) design, seeking to clarify the protective roles of albumin in the development of venous thrombosis.
Methods: We performed a bidirectional two-sample Mendelian randomization analysis utilizing albumin genome-wide association study (GWAS) data alongside VTE datasets from various sources. Additionally, to minimize heterogeneity across different datasets, a meta-analysis of the Mendelian randomization results was conducted. Furthermore, genes associated with such exposures were identified to unravel how exposure impacts outcomes. This was followed by applying bioinformatics techniques for gene enrichment analysis and employing the Cytoscape software to pinpoint the hub genes.
Results: The findings from the meta-analysis of the Mendelian randomization indicate that reduced levels of albumin are associated with an elevated risk of VTE (OR = 0.739, 95% CI: 0.695 to 0.787, P = 1.82e-9), DVT (OR = 0.700, 95% CI: 0.646 to 0.772, P = 2.96e-15), and PE (OR = 0.717, 95% CI: 0.647 to 0.793, P = 1.74e-10). Bioinformatics analysis revealed that serum albumin primarily protects against VTE by influencing inflammation and cytokines.
Conclusions: Our bidirectional MR analysis confirmed a substantial causal association linking serum albumin to VTE. Bioinformatics analysis revealed that this causal link is mediated by the immune response through inflammation and cytokines.