Arrhythmias & electrophysiology
Plasma Proteomic Insights for Identification of Novel Predictors and Potential Drug Targets in Atrial Fibrillation: A Prospective Cohort Study and Mendelian Randomization Analysis
Authors' conclusion
COL4A1 and RET are associated with the development of AF. RET is identified as a potential drug target for AF prevention, while COL4A1 serves as a biomarker for AF prediction.
Study context
- Population
- UK Biobank Pharma Proteomics Project participants; 2923 circulating proteins (Olink)
- Participants
- 38,784 participants
- Exposure
- Discovery vs Replication
- Outcome
- Incident AF, identified using International Classification of Diseases, Tenth Revision codes
Methodological detailsdiscovery and replication cohorts
- Discovery and replication cohorts
Main finding
As reported in the abstract
Proteins associated with incident AF and causal links (Mendelian randomization)
Odds ratio (95% CI)
COL4A1false discovery rate, 0.016; causal link with AF
1.11(1.04–1.19)
RETfalse discovery rate, 0.013; causal link with AF; druggable
0.96(0.94–0.98)
- Proteins linked to atrial fibrillation (AF) in both cohorts
- 21
Observational data: associations, not effects.
Further findings
Prediction of AF: COL4A1 added to established AF models (short and long term)
- Significant improvement in AUC, integrated discrimination improvement and net reclassification index
- P values below 0.05
Original publication
Plasma Proteomic Insights for Identification of Novel Predictors and Potential Drug Targets in Atrial Fibrillation: A Prospective Cohort Study and Mendelian Randomization Analysis. Circ Arrhythm Electrophysiol. Published 2 October 2024. doi:10.
Summarised from the published abstract; every number is checked against it