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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
PubMed

Insights

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.

Keywords:
Cardiovascular diseasesDifferent populationsDrug targetsProteomeTwo-sample Mendelian randomization

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