Causal Relationships between Lymphocyte Subsets and Risk of Coronary Artery Disease: A Two-Sample Mendelian
Zhao Ma1, Libo Liu1, Jinfan Tian1
1Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, 100029 Beijing, China.
Insights
Higher B cell counts are associated with increased risk of coronary artery disease (CAD) and myocardial infarction (MI). This Mendelian randomization study clarifies a potential causal link between B cells and cardiovascular disease.
Area of Science:
- Immunology
- Cardiovascular Genetics
- Epidemiology
Background:
- The causal relationship between lymphocyte subsets and coronary artery disease (CAD) is not well understood.
- Investigating immune cell involvement in CAD pathogenesis is crucial for understanding disease mechanisms.
Purpose of the Study:
- To assess the potential causal association between lymphocyte subsets and coronary artery disease (CAD) using Mendelian randomization (MR).
- To determine if specific immune cell counts influence the risk of developing CAD and myocardial infarction (MI).
Main Methods:
- A two-sample Mendelian randomization (MR) analysis was performed using publicly available genome-wide association study (GWAS) datasets.
- Inverse variance-weighted (IVW) method was the primary analysis, supplemented by MR-Egger, weighted median, simple mode, and weighted mode.
- Sensitivity analyses included Cochran's Q, MR-Egger intercept, MR-PRESSO, and leave-one-out analyses to assess heterogeneity, pleiotropy, and estimate robustness.
Main Results:
- A significant positive association was found between B cell count and CAD risk (OR = 1.08, p = 2.67 × 10⁻⁵) via the IVW method.
- Similarly, increased B cell count was associated with higher risk of myocardial infarction (MI) (OR = 1.07, p = 5.69 × 10⁻⁴).
- Sensitivity analyses confirmed no significant outliers, heterogeneity, or pleiotropy; reverse MR analysis showed no significant impact of CAD/MI on B cell count.
Conclusions:
- Higher absolute B cell counts are causally linked to an increased risk of coronary artery disease (CAD).
- The findings suggest a potential role for B lymphocytes in the development or progression of cardiovascular disease.
Background:
Currently, the causal relationship between lymphocyte subsets and coronary artery disease (CAD) remains unclear. Therefore, we utilized Mendelian randomization (MR) to assess the association between lymphocyte subsets and CAD.
Methods:
We performed a two-sample MR analysis using publicly available genome-wide association studies (GWAS) datasets. The primary method of analysis to comprehensively evaluate causal effects was the inverse variance-weighted (IVW) method. The four additional MR approaches were MR-Egger, weighted median, simple mode, and weighted mode. Sensitivity analysis incorporated Cochran's Q and MR-Egger intercept tests to identify residual heterogeneity and potential horizontal pleiotropy, respectively. The MR-PRESSO distortion test was applied to identify potential pleiotropic outliers. Leave-one-out analysis confirmed that no single single-nucleotide polymorphism (SNP) significantly affected the MR estimate. We conducted reverse MR analysis to investigate the impact of variables correlated with outcomes in forward MR analysis.
Results:
The IVW method revealed a significant positive association between B cell count and CAD (odds ratio (OR) = 1.08 (95% CI: 1.04, 1.11), p = 2.67 × 10-5). A similar association was observed between B cell count and myocardial infarction (MI) (OR = 1.07 (95% CI: 1.03, 1.11), p = 5.69 × 10-4). Sensitivity analyses detected no outliers, heterogeneity, or pleiotropy. The reverse MR analysis was conducted to investigate the impact of CAD and MI on B cell count, and the IVW results showed no statistical significance.
Conclusions:
Our study suggests that a higher absolute B cell count is linked to an increased risk of CAD and MI.
