Arrhythmias & electrophysiology
From blood to heartbeat: Plasma proteins and Brugada syndrome revealed by Mendelian randomization
Authors' conclusion
This study provides insight into the molecular landscape of BrS and identifies high-priority plasma proteins for further investigation. Experimental and clinical validation is needed to evaluate their diagnostic and therapeutic potential.
Study context
- Population
- Finnish cohort with pQTL proteomic data; Brugada syndrome (BrS)4,185 plasma proteins evaluated
- Exposure
- Causal associations between 4185 plasma proteins and BrS
- Outcome
- Plasma proteins potentially associated with BrS
Methodological detailsMendelian randomization (MR), pQTL proteomic data from a Finnish cohort, inverse variance weighted (IVW) method as primary analysis, MR-CAUSE, protein-protein interaction (PPI) networks, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, machine learning-based model to prioritize candidate proteins
- MR
- pQTL proteomic data from a Finnish cohort
- Inverse variance weighted (IVW) method as primary analysis
- MR-CAUSE
- Protein-protein interaction (PPI) networks
- Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses
- Machine learning-based model to prioritize candidate proteins
Main finding
As reported in the abstract
Plasma proteins identified as potentially associated with BrS
20
Observational data: associations, not effects.
Further findings
Sensitivity analyses
- Sensitivity analyses supported the robustness of these findings
Top candidate proteins
- HSPB1, MAPKAPK2, PDLIM4, and MMP1 emerged as top candidates based on causal strength, biological relevance, and network centrality
Original publication
From blood to heartbeat: Plasma proteins and Brugada syndrome revealed by Mendelian randomization. Heart Rhythm. Published 9 October 2025. doi:10.
Summarised from the published abstract; every number is checked against it