ArticleThrombosis journal2025
Causal association between circulating α-Klotho levels and venous thromboembolism: a two-sample Mendelian randomization study.
Article in Thrombosis journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundα-Klotho may involve in the occurrence and development of venous thromboembolism (VTE). However, the underlying relationship between circulating α-Klotho levels and VTE is still unclear.
methodsThis two-sample Mendelian Randomization (MR) study aims to explore the causal associations of circulating α-Klotho levels with different types of venous thromboembolism. Data of exposure and outcomes were extracted from the genome-wide association study (GWAS) of the MRC Integrative Epidemiology Unit (MRC-IEU). The fixed inverse variance weighted (IVW), MR-Egger, MR-Robust Adjusted Profile Score (RAPS) and the weighted-median methods were utilized to investigate the causal associations of circulating α-Klotho levels with different types of VTE. The effect size was expressed as odds ratios (ORs) and 95% confidence intervals (CIs), and the False Discovery Rate (FDR) test was used for correction. The MR scatter plot and leave-one-out test were used for sensitivity analysis. In addition, reverse causal associations were assessed.
resultsIVW estimates suggested that an elevated circulating α-Klotho level was associated with lower odds of deep vein thrombosis (DVT) of lower extremities (OR = 0.992, 95%CI: 0.986-0.998, P = 0.0074), pulmonary embolism (PE) (OR = 0.474, 95%CI: 0.255-0.881, P = 0.0183), and DVT of lower extremities combined with PE (OR = 0.984, 95%CI: 0.971-0.997, P = 0.0175). However, after the FDR correction, only negatively causal association between circulating α-Klotho level and increased odds of lower-extremity DVT was statistically significant (FDR P = 0.0296). Also, there were no reverse causal associations between the circulating α-Klotho levels and different types of VTE (all P > 0.05). Additionally, both the MR scatter plots and leave-one-out test results showed that these causal associations were relatively robust.
conclusionAn elevated circulating α-Klotho levels was associated with lower risk of DVT of lower extremities, PE, and DVT of lower extremities combined with PE, indicating α-Klotho has the potential to act as a target for early screening or treatment for VTE. However, the specific mechanism that α-Klotho influencing the occurrence of VTE still needed further exploration.
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