Genetic Association of Circulating Proteins and Gene Transcripts With Spontaneous Coronary Artery Dissection

Area of Science:

• Genetics
• Proteomics
• Cardiovascular Research

Background:

• Spontaneous coronary artery dissection (SCAD) is an uncommon cause of myocardial infarction, predominantly affecting women.
• The pathophysiology of SCAD remains poorly understood, limiting effective prevention and treatment strategies.

Purpose of the Study:

• To investigate the genetic associations between circulating proteins and SCAD risk.
• To explore the role of tissue-specific gene expression in SCAD pathogenesis.
• To identify potential causal proteins and pathways involved in SCAD.

Main Methods:

• Utilized Mendelian randomization and Bayesian colocalization to analyze genetic associations.
• Derived genetic scores for over 1500 circulating proteins and 13,000 gene transcripts.
• Conducted a genome-wide association study meta-analysis and in vitro proteomic validation.

Main Results:

• Identified four circulating proteins genetically associated with SCAD: AFAP1, ECM1, SPON1, and STAT6.
• ECM1 was supported by gene expression and colocalization analyses, and significantly upregulated in SCAD patients.
• Protein interaction mapping suggested roles in JAK-STAT signaling and inflammation.

Conclusions:

• Integrative analysis revealed ECM1 as a key protein with a likely causal role in SCAD pathogenesis.
• Findings highlight potential biological pathways and protein targets for SCAD therapeutic interventions.
• This research provides a foundation for further mechanistic studies into SCAD.