Immune cells and rheumatic heart disease: A 2-sample and Bayesian weighted Mendelian randomization study

Using Mendelian randomization (MR) analysis to explore the immune cells involved in rheumatic heart disease (RHD). We conducted a bidirectional 2-sample MR study to screen the causal effects of 731 immune cell phenotypes on RHD. MR analysis was performed using regression models including inverse variance weighting, MR-Egger method, simple mode method, weighted median method, and weighted mode method. At the same time, heterogeneity tests, horizontal pleiotropy analysis, and sensitivity analyses were performed to verify the reliability of the MR results. Finally, to estimate causal effects under multiple hypotheses and improve the reliability of causal inference, we used the Bayesian weighted Mendelian randomization method to validate the results of the MR study. First, the results of MR showed that there was a causal relationship between 10 immune cell phenotypes and RHD, among which CD19 on CD20-, HVEM on TD CD4, CD40 on monocytes, CD45 on CD33- HLA DR-, CD11b on CD33br HLA DR+, CD14dim were risk factors for RHD, and CD24 on IgD+, CD24+, CD38 on CD3-, CD19-, CX3CR+, and CX3CR+. CD19-, CX3CR1 on CD14- CD16+ monocyte, CD14 on CD33dim HLA DR+, CD11b+, SSC-A on lymphocyte is a protective factor for RHD. Second, the results of reverse MR showed that RHD was not the influencing factor of the 10 positive immune cell phenotypes screened. Third, Bayesian weighted Mendelian randomization excluded CD40 on monocytes and CX3CR1 on CD14- CD16+ monocyte. The remaining results were the same as those of the 2 samples for MR analysis. This study confirmed the close relationship between immune cells and RHD through genetics. This study confirms the close association between immune cells and RHD by genetic means and provides a reference for future studies.