Causal Relationships between Lymphocyte Subsets and Risk of Coronary Artery Disease: A Two-Sample Mendelian Randomization Study.

Abstract

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.