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Cross-population proteome-wide mendelian randomization study identifies likely causal proteins for cardiovascular
Hua Zhong1,2,3, Jingjing Zhu1,2,4, Shuai Liu1,2,3
1Department of Interdisciplinary Oncology, LSU-LCMC Health Cancer Center, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
Molecular Genetics and Genomics : MGG
|August 3, 2026
Summary
Proteome-wide Mendelian randomization identified 53 protein-cardiovascular disease links across diverse populations. This research highlights population-specific associations and prioritizes 14 targets for drug development, advancing precision medicine.
Area of Science:
- Genetics
- Cardiovascular Medicine
- Proteomics
Background:
- Cardiovascular diseases (CVDs) like heart failure (HF) and peripheral artery disease (PAD) are linked to blood proteins.
- Proteome-wide Mendelian randomization (MR) is valuable for identifying drug targets in European populations but is underutilized in others.
- Limited research exists on the causal roles of plasma proteins in CVDs across diverse ethnic groups.
Purpose of the Study:
- To investigate the causal relationships between 2,922 plasma proteins and five CVDs (atrial fibrillation, coronary artery disease, HF, ischemic heart disease, PAD) using a multi-population approach.
- To identify population-specific protein-CVD associations and potential drug targets for therapeutic development or repurposing.
- To assess the utility of proteome-wide MR in diverse populations for advancing precision medicine in cardiovascular care.
Main Methods:
- Conducted a proteome-wide MR analysis across African, East Asian, and European populations.
- Utilized genetic instrument data from the UK Biobank cohort for 2,922 plasma proteins and five CVDs.
- Employed genetic colocalization to validate significant MR associations and strengthen causal inference.
Main Results:
- Identified 53 significant protein-CVD associations across the studied populations.
- Discovered 16 associations in the African, six in the East Asian, and 31 in the European populations.
- Found four protein-CVD associations unique to the African population and four unique to the East Asian population.
- Prioritized 14 protein-disease pairs as promising candidates for drug development or repurposing through integration with clinical trial data.
Conclusions:
- Proteome-wide MR is a valuable tool for identifying drug targets for CVDs across diverse populations.
- Population-specific protein-CVD associations underscore the need for inclusive genetic research.
- Findings support the development of precision medicine strategies for CVD prevention and treatment.
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