Plasma Proteomics to Identify Drug Targets for Ischemic Heart Disease
Authors' conclusion
Integrated analyses of proteomic and genetic data in Chinese and European adults provided causal support for FURIN and multiple other proteins as potential novel drug targets for treatment of IHD.
Study context
- Population
- Genotyped Chinese adults free of prior CVD (China Kadoorie Biobank); Mendelian randomization (MR) in CARDIOGRAM+C4D (210,842 ischemic heart disease (IHD) cases and 1,378,170 controls)
- Participants
- 1,971 vs 2,001
- Exposure
- IHD cases vs Subcohort
- IHD casesn = 1,971
- Subcohortn = 2,001reference
- Outcome
- Associations of plasma proteins with incident IHD
Methodological details2-sample Mendelian randomization, China Kadoorie Biobank, OLINK EXPLORE panel (1,463 proteins)
- 2-sample Mendelian randomization
- China Kadoorie Biobank
- OLINK EXPLORE panel (1,463 proteins)
Main finding
As reported in the abstract
- Proteins significantly associated with IHD risk (FDR <0.05), incl. NT-proBNP and PCSK9
- 361
- Positively associated
- 349
- Inversely associated
- 12
- Proteins with cis-pQTLs in China Kadoorie Biobank (CKB)
- 212
- Proteins with potentially causal associations with IHD (MR of 198 variants in CARDIOGRAM+C4D)
- 13
- Proteins replicated in independent MR of 307 cis-pQTLs in Europeans (FURIN, PAR-1, ASGR1, MMP-3)
- 4
Observational data: associations, not effects.
Further findings
Downstream analyses
- FURIN (highly expressed in endothelial cells) a potential novel target; MMP-3 a potential repurposing target for IHD
Original publication
Plasma Proteomics to Identify Drug Targets for Ischemic Heart Disease. J Am Coll Cardiol. Published 14 November 2023. doi:10.
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