Comprehensive two-sample Mendelian randomization analysis of blood cell perturbation phenotypes and heart failure

Abstract

Background: The causal relationships between blood cell perturbation phenotypes and heart failure (HF) remain unclear. This study aimed to investigate these potential associations using two-sample Mendelian randomization (MR). Methods: A two-sample MR analysis was performed using genome-wide association study summary statistics, with 91 blood cell perturbation phenotypes as exposures and HF as the outcome. The inverse-variance weighted method was used as the primary causal estimation method, supplemented by sensitivity analyses to assess the robustness of the results. A P value < 0.05 was considered statistically significant. Results: MR analysis identified eight blood cell perturbation phenotypes with nominally significant suggestive associations with HF ( P < 0.05). However, none of these associations survived Bonferroni correction for multiple testing (α = 0.05/91 = 0.00055). Sensitivity analyses confirmed robustness, with no evidence of pleiotropy or heterogeneity. These hypothesis-generating findings require validation in independent cohorts with appropriate multiple testing correction. Conclusion: This study provides suggestive evidence that 8 blood cell perturbation phenotypes may have potential causal associations with HF.