Key Takeaways & Executive Findings
- •• Five immune cell phenotypes were causally associated with atrial fibrillation risk, including CD11c on monocytes and CX3CR1 on monocyte subsets. • Three immune phenotypes (CD19 on switched memory B cells, CD25++CD8+ T cells, and their absolute count) were protective against hypertension. • No significant heterogeneity or horizontal pleiotropy was detected in sensitivity analyses, supporting the robustness of the causal estimates. • The findings suggest that immune cell phenotypes may serve as potential targets for monitoring and treating atrial fibrillation and hypertension.
Abstract
BACKGROUND: Previous studies have linked immune cells to cardiovascular disease risk. As confounding factors are incompletely addressed, the causal relationship between them remains unclear. OBJECTIVE: To evaluate the potential causal relationship between immune cells and cardiovascular disease. METHODS: The source of research data mainly involves three databases: Genome-Wide Association Study (GWAS) database (GWAS Catalog, jointly maintained by the National Institute of Human Genomics and the European Institute of Bioinformatics), UK biobank (a database of British population genomics, health, and disease phenotypes supported by the UK government and the Wellcome Trust), and IEU OpenGWAS (a GWAS database developed by the MRC Epidemiology Unit at the University of Bristol, UK, primarily for European populations). All are open databases, and the study has been approved by the relevant institutional review boards. Using 731 immune cell phenotypes as exposures and 7 cardiovascular diseases (atrial fibrillation, dilated cardiomyopathy, coronary atherosclerotic heart disease, heart failure, hypertrophic cardiomyopathy, hypertension, and valvular heart disease) as outcomes, a two-sample Mendelian randomization analysis was performed. Inverse variance weighting and weighted median methods were mainly used for Mendelian randomization analysis and sensitivity analysis to assess heterogeneity and pleiotropy. RESULTS AND CONCLUSION: (1) After false discovery rate correction, immune phenotypes had statistically significant effects on atrial fibrillation and hypertension. Five cell types were associated with atrial fibrillation risk, including CD11c on monocytes (OR=0.917, 95%CI: 0.876-0.960), FSC-A on myeloid dendritic cells (OR=0.942, 95%CI: 0.910-0.974), CX3CR1 on CD14+ CD16- monocytes (OR=1.045, 95%CI: 1.022-1.070), CX3CR1 on monocytes (OR=1.050, 95%CI: 1.024-1.076), and CX3CR1 on CD14+ CD16+ monocytes (OR=1.050, 95%CI: 1.024-1.077). Three immune phenotypes with protective effects on hypertension were identified: CD19 on switched memory B cells (OR=0.986, 95%CI: 0.980-0.993), CD25++CD8+ T cells (OR=0.993, 95%CI: 0.990-0.997), and CD25++CD8+ T cells absolute count (OR=0.993, 95%CI: 0.989-0.996). No potential heterogeneity or horizontal pleiotropy was observed in sensitivity analyses. (2) The study found causal relationships between 4 monocyte types and 1 myeloid dendritic cell type and atrial fibrillation, and potential causal relationships between 1 memory B cell type and 2 T cell types and hypertension, suggesting the necessity of considering immune cell phenotypes when monitoring and treating atrial fibrillation and hypertension. This study used public databases for analysis, providing a reference for research on immune cell subsets and cardiovascular disease in the Chinese population, and offering insights for further prevention and treatment of atrial fibrillation and hypertension in Chinese people.
1. Introduction
Cardiovascular disease is a collective term for diseases of the heart and blood vessels. Despite significant advances in cardiovascular research in recent decades, it remains a leading cause of death and disability among non-communicable diseases globally [1-3]. In 2020, approximately 19 million people died from cardiovascular disease worldwide, an 18.7% increase from 2010 [4]. Mortality rates vary considerably by region; European data indicate that Eastern European men and women have the highest proportions of cardiovascular-related deaths (48% and 57%, respectively), while Western European men have the lowest (29%) [5]. According to the American Heart Association, cardiovascular disease treatment costs in the United States increased by $122.7 billion between 1996 and 2018 [4]. Similar to global trends, China faces a severe cardiovascular disease prevention and control situation [6-7]. Thus, cardiovascular disease poses a serious threat to public health and imposes a significant economic burden on society.
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Huang Zhe, Shang Baoling, Yao Gengzhen, Pan Guangming (2026). Association between immune cells and cardiovascular disease risk: a genome-wide association study in European populations. Chinese Journal of Tissue Engineering Research. https://doi.org/10.12307/2026.21263
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Frequently Asked Questions
What was the main objective of this study?
The main objective was to evaluate the potential causal relationship between immune cell subtypes and cardiovascular disease using Mendelian randomization.
Which cardiovascular diseases were included in the analysis?
The study included seven cardiovascular diseases: atrial fibrillation, dilated cardiomyopathy, coronary atherosclerotic heart disease, heart failure, hypertrophic cardiomyopathy, hypertension, and valvular heart disease.
What were the key findings regarding atrial fibrillation?
Five immune cell phenotypes were found to be causally associated with atrial fibrillation risk, including CD11c on monocytes, FSC-A on myeloid dendritic cells, and CX3CR1 on monocyte subsets.
What were the key findings regarding hypertension?
Three immune phenotypes were identified as protective against hypertension: CD19 on switched memory B cells, CD25++CD8+ T cells, and their absolute count.
How were the causal relationships assessed?
The study used two-sample Mendelian randomization with inverse variance weighting and weighted median methods, along with sensitivity analyses to assess heterogeneity and pleiotropy.
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