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

Abstract

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. 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. 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. Our study suggests that a higher absolute B cell count is linked to an increased risk of CAD and MI.