Immune cells and rheumatic heart disease: A 2-sample and Bayesian weighted Mendelian randomization study
Siyang Xue1,2, Hongju Jiang1, Chenfei Liu2
1Department of Cardiology, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.
Medicine
|March 27, 2026
Summary
This study used genetic analysis to identify immune cells influencing rheumatic heart disease (RHD). Several immune cell types were found to be risk factors or protective against RHD, confirming a genetic link.
Area of Science:
- Immunology
- Genetics
- Cardiovascular Disease Epidemiology
Background:
- Rheumatic heart disease (RHD) is a significant global health concern with complex etiology.
- The role of specific immune cell phenotypes in RHD pathogenesis remains incompletely understood.
- Genetic associations can elucidate causal relationships between biological factors and disease.
Purpose of the Study:
- To investigate the causal effects of various immune cell phenotypes on the risk of developing rheumatic heart disease (RHD) using Mendelian randomization.
- To identify specific immune cell populations that act as risk factors or protective elements in RHD.
- To explore the potential reverse causality from RHD to immune cell phenotypes.
Main Methods:
- A bidirectional two-sample Mendelian randomization (MR) study was conducted.
- Genome-wide association study (GWAS) data for 731 immune cell phenotypes and RHD were utilized.
- Multiple MR methods (inverse variance weighting, MR-Egger, etc.) and Bayesian weighted MR were employed for robust causal inference.
- Heterogeneity, pleiotropy, and sensitivity analyses were performed to ensure result validity.
Main Results:
- MR analysis identified 10 immune cell phenotypes with a causal relationship to RHD.
- Specific immune cells, including CD19 on CD20-, HVEM on TD CD4, and CD40 on monocytes, were identified as risk factors.
- Other immune cells, such as CD24 on IgD+ and CD14 on CD33dim HLA DR+, were found to be protective against RHD.
- Reverse MR analysis indicated no significant causal effect of RHD on the identified immune cell phenotypes.
- Bayesian weighted MR validated most findings, excluding CD40 on monocytes and CX3CR1 on CD14- CD16+ monocyte.
Conclusions:
- This genetic study confirms a significant association between specific immune cell phenotypes and rheumatic heart disease (RHD).
- The findings highlight potential causal pathways involving immune cells in RHD development.
- This research provides a genetic reference for future investigations into RHD etiology and therapeutic targets.
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