A Southern African Map of Blood Regulatory Variation Enables GWAS Interpretation

Abstract

Functional genomics resources are critical for interpreting human genetic studies, however they are predominantly from European-ancestry individuals. Here we present the Southern African Blood Regulatory (SABR) resource, a map of blood regulatory variation that includes three South Eastern Bantu-speaking groups. Using paired whole genome and blood transcriptome data from over 600 individuals, we map the genetic architecture of 40 blood cell traits derived from deconvolution analysis, as well as expression, splice, and cell type interaction quantitative trait loci. We comprehensively compare SABR to the Genotype Expression (GTEx) Project and characterize the thousands of African-enriched and African-specific regulatory variants mapped. Finally, we demonstrate the increased utility of SABR for interpreting African association studies by identifying putatively causal genes and molecular mechanisms through colocalization analysis of 83 blood-relevant traits from the PAN-UK Biobank. Importantly, we make full SABR summary statistics publicly available to support the African genomics community.