Multi-trait GWAS reveals divergent local and polygenic architecture of cardiovascular traits across African and European ancestries in the UK Biobank

Abstract

The genetic architecture of cardiovascular traits is poorly characterised in non-European populations, limiting our understanding of disease aetiology and contributing to health disparities. Here, we analyse the genetic architecture of four cardiovascular traits (systolic and diastolic blood pressure, pulse rate, and maximum heart rate) using multi-trait analysis of genome-wide association studies and local genetic correlation analysis in 459,327 European (EUR) and 6654 African (AFR) ancestry individuals from the UK Biobank. Our analysis identifies 957 and 45 novel variants in the EUR and AFR cohorts, respectively, but reveals a profound divergence in the pleiotropic architecture of blood pressure. We identify 181 genomic loci with significant local genetic correlation between systolic and diastolic blood pressure (SBP-DBP) in the European sample, whereas such signals are completely absent in the African ancestry cohort. This marked disparity in local genetic correlation structure highlights that pleiotropic mechanisms can be highly ancestry-specific, underscoring the limitations of transferring genetic risk models across populations and the critical need for inclusive genomic research.