Abstract
This study sought to explore the causal pathways and mediating effects of sociopsychosocial factors on chronic coronary artery syndrome (CCS) from a genetic variation perspective. The Mendelian randomization approach was used to investigate the causal effects of sociopsychological factors (including anxiety, depression, constipation, diarrhea, nausea and vomiting, social deprivation, and family income) on chronic coronary syndrome. For the analysis, the TwoSampleMR, MR-PRESSO, multivariable Mendelian randomization (MVMR), and forestploter packages in R software were employed. The inverse variance weighting method was the primary approach for evaluation of the causal estimates. Anxiety, depression and diarrhea exhibit significant positive causal associations with CCS (P = .022, P = .001, P = .000). Household income demonstrated a significant negative causal relationship with CCS (P = .014). Furthermore, even after adjusting for anxiety, depression remained significantly and positively associated with CCS (P = .028). The mediators implicated in these causal pathways encompass TNF-related apoptosis-inducing ligand (TRAIL), low density lipoprotein (LDL), triglycerides (TG), and smoking initiation. A total of 8 significant mediation pathways were identified involving sociopsychosocial factors, mediator variables, and CCS (proportion of mediating effects): anxiety → smoking initiation → CCS (10.26%), anxiety → TRAIL → CCS (6.67%), anxiety → LDL → CCS (35.86%), major depressive disorder (MDD) → TRAIL → CCS (7.38%), MDD → LDL → CCS (34.20%), family income → smoking initiation → CCS (12.83%), family income → LDL → CCS (20.99%), and family income → TG → CCS (20.64%). Anxiety, depression, and diarrhea were linked to an increased risk of CCS, while higher family income was associated with a lower risk. These factors also showed indirect effects on CCS through smoking behavior, inflammation, and blood lipid levels, offering a theoretical basis for future clinical research.