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Causal Association Between Idiopathic Pulmonary Fibrosis and Coronary Artery Disease: A Bidirectional Two-Sample
Lirui Yang1, Xin Zhao1, Tingting Feng1
1Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, 101118 Beijing, China.
Summary
Coronary artery disease (CAD) may genetically reduce the risk of idiopathic pulmonary fibrosis (IPF). This Mendelian randomization study found a significant inverse genetic association between CAD and IPF risk.
Area of Science:
- Cardiovascular Genetics
- Pulmonary Medicine
- Genetic Epidemiology
Background:
- Epidemiological links exist between coronary artery disease (CAD) and idiopathic pulmonary fibrosis (IPF).
- The underlying genetic basis for this association is not well understood.
- Investigating causal relationships is crucial for understanding disease pathogenesis.
Purpose of the Study:
- To explore potential causal relationships between IPF and CAD.
- To utilize a bidirectional two-sample Mendelian randomization (MR) approach.
- To clarify the genetic underpinnings of the observed epidemiological link.
Main Methods:
- Employed bidirectional two-sample Mendelian randomization (MR).
- Utilized summary statistics from genome-wide association studies for CAD and IPF.
- Applied inverse-variance weighted (IVW), MR-Egger, weighted median, and weighted mode methods.
- Assessed heterogeneity and pleiotropy using Cochran's Q test, MR-Egger regression, and MR-PRESSO.
- Validated findings with leave-one-out analysis.
Main Results:
- Forward MR analysis showed no significant genetic causal link between IPF and CAD (OR = 0.989, p = 0.305) after outlier removal.
- Reverse MR analysis revealed a significant negative genetic causal association of CAD with IPF risk (OR = 0.832, p = 0.023).
- Sensitivity analyses confirmed heterogeneity was resolved and detected no horizontal pleiotropy.
Conclusions:
- Coronary artery disease (CAD) may exert a negative genetic influence on the risk of idiopathic pulmonary fibrosis (IPF).
- Findings offer insights for developing improved preventive and therapeutic strategies.
- Further research on CAD-IPF interactions is recommended for enhanced disease management.
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