The genetic causal relationships of membranous nephropathy and serum albumin concentrations with the risk of developing venous thromboembolism, pulmonary embolism, and deep-vein thrombosis of the lower extremities: A two-sample Mendelian randomization study

Abstract

Background The aim of this study was to explore the genetic-level associations of membranous nephropathy and serum albumin concentrations with the risk of developing venous thromboembolism(VTE), encompassing deep-vein thrombosis of the lower extremities and pulmonary embolism(PE), using bidirectional two-sample Mendelian randomization (MR) analysis. Methods Using summary-level data from large-scale genome-wide association studies (GWASs) in European individuals, in this study, MR was employed to examine potential causal relationships between several exposures (MN status and serum albumin concentrations) and outcomes (VTE, DVT of the lower extremities, PE). Two-sample MR analyses were conducted utilizing the TwoSampleMR and MRPRESSO packages within the R programming environment. Inverse-variance weighting (IVW) was used as the primary method for MR analysis. In addition, MR‒Egger, weighted median, weighted mode and MR–pleiotropy residual sum and outlier (MR–PRESSO) were used for complementary analyses. Furthermore, a series of sensitivity analyses were performed to ensure the validity and robustness of the results. Results The random-effects IVW analysis revealed a negative genetic causal association between serum albumin concentrations and the risk of developing DVT of the lower extremities (OR: 0.757, 95% CI: 0.574–0.999, P = 0.049), as well as between serum albumin concentrations and the risk of developing VTE (OR: 0.798, 95% CI: 0.659–0.966, P = 0.021). Conversely, the random-effects IVW analysis did not reveal a genetic causal relationship between serum albumin concentrations and the risk of developing PE (P > 0.05). However, genetically predicted MN status was not associated with the risk of developing VTE, DVT of the lower extremities or PE. Conclusion Our investigation revealed that serum albumin concentrations exhibit negative genetic-level causal relationships with the risk of developing VTE and DVT of the lower extremities, while two-sample MR analysis did not reveal genetic evidence supporting a significant association between MN and the risk of experiencing TE events (VTE, DVT of the lower extremities, PE).