Related Experiment Video
Updated: Jun 19, 2025
Catheter Ablation in Combination With Left Atrial Appendage Closure for Atrial Fibrillation
Published on: February 26, 2013
Fibroblast growth factor 5 as a target for atrial fibrillation treatment: Evidence from mendelian randomization
Chenxi Gao1, Wenyu Wang2, He Jia1
1First hospital of Jilin University, Changchun, Jilin, China.
Background:
Previous studies have found that inflammatory proteins are involved in the pathogenesis of atrial fibrillation (AF). We used mendelian randomization to explore the potential pathogenic inflammatory proteins of AF.
Methods:
This study adopts a Mendelian randomization design to primarily assess causal associations using the Wald ratio and the inverse variance weighting method. It leverages protein quantitative trait locus (pQTL) data encompassing 91 types of inflammatory proteins from 14,824 participants of European ancestry. The primary analysis phase utilizes AF GWAS data from 55,106 participants, with an additional 237,690 participants included in the validation stage. Sensitivity analyses, including reverse causality analysis, Bayesian colocalization analysis, and phenotype scanning, were conducted. Finally, the study explores potential targeted drugs.
Results:
The findings highlight a causal link between 7 inflammatory proteins and AF, with 2 showing positive correlations and 5 exhibiting negative correlations. Among these, fibroblast growth factor 5 (FGF5) emerges as particularly robust in sensitivity analysis. Colocalization analysis indicates a shared genetic variation between FGF5 and AF, supporting its potential as a targeted therapy for AF. Importantly, this causal relationship remains unaffected by reverse causality. Furthermore, significant pleiotropic effects were observed in phenotype scanning. Finally, the causal association between FGF5 and AF was successfully replicated during the validation phase.
Conclusion:
FGF5 may become an intervention target for AF targeted therapy.
Insights
This study identified seven inflammatory proteins causally linked to atrial fibrillation (AF). Fibroblast growth factor 5 (FGF5) shows strong potential as a therapeutic target for AF.
Area of Science:
- Cardiovascular Research
- Genetics
- Immunology
Background:
- Inflammatory proteins are implicated in the development of atrial fibrillation (AF).
- Mendelian randomization is employed to investigate potential causal links between inflammatory proteins and AF pathogenesis.
Purpose of the Study:
- To explore causal associations between inflammatory proteins and atrial fibrillation (AF) using a Mendelian randomization approach.
- To identify specific inflammatory proteins that may serve as therapeutic targets for AF.
Main Methods:
- Utilized Mendelian randomization with Wald ratio and inverse variance weighting.
- Analyzed protein quantitative trait locus (pQTL) data for 91 inflammatory proteins in European ancestry participants.
- Employed large-scale atrial fibrillation genome-wide association study (AF GWAS) data for primary analysis and validation.
- Conducted sensitivity analyses including reverse causality and colocalization.
Main Results:
- Identified a causal relationship between seven inflammatory proteins and AF.
- Two proteins showed positive correlation, and five showed negative correlation with AF.
- Fibroblast growth factor 5 (FGF5) demonstrated a robust causal link with AF, supported by colocalization and unaffected by reverse causality.
- Validation phase confirmed the causal association between FGF5 and AF.
Conclusions:
- Fibroblast growth factor 5 (FGF5) is a potential therapeutic target for atrial fibrillation (AF).
- Targeting FGF5 may offer a novel strategy for AF intervention.
