Causal Association Between Idiopathic Pulmonary Fibrosis and Coronary Artery Disease: A Bidirectional Two-Sample...

Coronary artery disease (CAD) has been epidemiologically linked to idiopathic pulmonary fibrosis (IPF); however, the genetic basis of this association remains unclear. Therefore, this study aims to investigate the potential causal relationships between IPF and CAD using a bidirectional two-sample Mendelian randomization (MR) strategy.

Inverse-variance weighted (IVW), MR-Egger, weighted median, and weighted mode approaches were applied to summary statistics obtained from CAD and IPF genome-wide association studies. Heterogeneity among instrumental variables was assessed using Cochran's Q test. Pleiotropy was assessed using MR-Egger regression and MR pleiotropy residual sum and outlier (MR-PRESSO) analyses. Additionally, the robustness and reliability of the findings were validated by applying a leave-one-out analysis.

The forward MR analysis revealed no evidence supporting a genetic causal association between IPF and CAD (odds ratio [OR] = 0.989, 95% confidence interval [CI]: 0.967-1.010, p = 0.305) after excluding an outlier single-nucleotide polymorphism (SNP) (rs7725218). However, reverse MR analysis demonstrated a significant negative genetic causal association between CAD and IPF (OR = 0.832, 95% CI: 0.711-0.975, p = 0.023). Sensitivity analysis revealed heterogeneity in the forward MR analysis, which was resolved after excluding an outlier SNP, with no evidence of horizontal pleiotropy detected.

This study demonstrates a potential negative genetic influence of CAD on the risk of IPF, providing valuable insights that may guide the development of more enhanced preventive and therapeutic strategies. Future research should further assess the interactions between CAD and IPF to improve disease management and patient outcomes.