Cross-Ancestry Proteogenomic Analyses Identified New Therapeutic Insights for Ischemic Heart Disease
Authors' conclusion
The findings support a role for lipid-driven chronic inflammation in IHD etiology
Study context
- Population
- Statin-free individuals in the prospective China Kadoorie Biobank (CKB); Mendelian randomization (MR) in East Asians, replication in Europeans1,976 cases · 2,001 subcohort controls
- Outcome
- Potential drug targets for ischemic heart disease (IHD), from cis-pQTLs for plasma proteins
Methodological detailscross-ancestry proteogenomic analysis, case-cohort, two-sample Mendelian randomization, colocalization analyses, replication in Europeans, 9,520 plasma proteins measured (Olink/SomaScan: 2,923/7,297); 2,895 cis-pQTLs identified, MR in East Asians (n = 29,319 cases); replication in Europeans (n = 181,522 cases)
- Cross-ancestry proteogenomic analysis
- Case-cohort
- Two-sample Mendelian randomization
- Colocalization analyses
- Replication in Europeans
- 9,520 plasma proteins measured (Olink/SomaScan: 2,923/7,297); 2,895 cis-pQTLs identified
- MR in East Asians (n = 29,319 cases); replication in Europeans (n = 181,522 cases)
Main finding
As reported in the abstract
Proteins with evidence for a role in IHD
- Proteins associated with ischemic heart disease (IHD) in CKB observational analyses (FDR-corrected P < 0.05; Olink/SomaScan: 426/533)
- 959
- Proteins with genetic support in IHD etiology by two-sample MR (Olink/SomaScan: 36/28)
- 54
- Proteins with colocalization (PPH4 ≥0.8) in East Asians: 8 lipid-, 3 inflammation-, 1 BP- and 3 alcohol-related (Olink/SomaScan: 10/10)
- 15
- Europeans: of 12 non-alcohol-related proteins, directionally concordant MR results
- 8
- Europeans: directionally discordant MR results (incl. APOA5, SORT1, transforming growth factor beta 1 with strong colocalization)
- 4
Observational data: associations, not effects.
Further findings
Comparison with previous MR studies
- Little consistency in number and identity of target proteins beyond established lipid-related (LDL-C, lipoprotein(a), TG) or inflammation-related (interleukin-6) targets
Original publication
Cross-Ancestry Proteogenomic Analyses Identified New Therapeutic Insights for Ischemic Heart Disease. J Am Coll Cardiol. Published 29 July 2026. doi:10.
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