We are thrilled to highlight a new publication in Circulation: Genomic and Precision Medicine, authored entirely by members of our CERC community: Phenome-Wide Mendelian Randomization Identifying Circulating Proteins for Cardiovascular Traits in Populations of African Ancestry. This collaborative achievement underscores the program’s commitment to advancing equitable, genomics‑driven insights for global populations.
The article, “Phenome‑Wide Mendelian Randomization Identifying Circulating Proteins for Cardiovascular Traits in Populations of African Ancestry,” presents a rigorous and high‑resolution investigation of proteomic determinants of cardiometabolic disease, with a focus on populations historically underrepresented in genetic research.
About the Study
This study addresses a longstanding limitation in genomic medicine: the heavy bias toward discoveries in European‑ancestry cohorts. Using 2‑sample Mendelian randomization and colocalization analyses, the authors evaluated 1,562 circulating proteins across 145 cardiometabolic traits in individuals of African ancestry.
They then cross‑validated significant findings using large‑scale proteomic resources from the UK Biobank Pharma Proteomics Project, and further assessed whether signatures of natural selection may drive population‑specific protein–phenotype associations.
Key Discoveries
The team identified 115 robust protein–outcome associations in African‑ancestry populations, 51 of which differed significantly from European‑ancestry estimates—demonstrating ancestry‑specific biological effects that would have been overlooked in Euro‑centric datasets.
Four proteins—CD36, APOC1, GSTA1, and FOLH1—emerged as particularly compelling cardiometabolic targets, influencing lipid levels and heart‑related conditions in ways uniquely detectable in African‑ancestry cohorts.
The authors show that nearly 47.5% of these associations may be shaped by cis‑acting pQTLs under natural selection, highlighting evolutionary pressures as an underappreciated factor in precision medicine.
These findings not only broaden the catalog of actionable protein targets but also reveal how population‑specific variation can reshape the landscape of drug discovery, risk prediction, and mechanistic understanding of cardiometabolic disease.
Why This Matters for Precision Medicine
This research exemplifies why genomic diversity is essential for developing equitable therapies. Ancestry‑aware analyses can identify biomarkers and therapeutic targets that benefit patient groups routinely excluded from large‑scale studies—supporting the development of treatments that work for everyone, not just the populations most represented in research.
CERC Team Contribution
All authors of this publication are members of the Canada Excellence Research Chair in Genomic Medicine program. Their collective expertise—spanning proteomics, statistical genetics, cardiometabolic genomics, and evolutionary biology—made it possible to produce this ambitious and impactful analysis.
This work represents yet another step forward in CERC’s mission to integrate multi‑omics, population genetics, and precision health for global impact.