The African Genome Variation Project shapes medical genetics in Africa

TLDR

Africa’s genetic diversity is crucial for studies of human origins and disease susceptibility, and the African Genome Variation Project supplies a resource to design, implement, and interpret genomic studies across sub‑Saharan Africa and globally. The project includes dense genotypes from 1,481 individuals and whole‑genome sequences from 320 individuals across sub‑Saharan Africa, and it presents an efficient genotype array design that captures common genetic variation in the region. Using the resource, the study reveals complex, regionally distinct hunter‑gatherer and Eurasian admixture, identifies new loci under selection related to malaria susceptibility and hypertension, shows that modern imputation panels can detect association signals at highly differentiated loci, and demonstrates that whole‑genome sequencing further improves imputation accuracy, underscoring the value of large‑scale sequencing of diverse African haplotypes.

Abstract

Given the importance of Africa to studies of human origins and disease susceptibility, detailed characterization of African genetic diversity is needed. The African Genome Variation Project provides a resource with which to design, implement and interpret genomic studies in sub-Saharan Africa and worldwide. The African Genome Variation Project represents dense genotypes from 1,481 individuals and whole-genome sequences from 320 individuals across sub-Saharan Africa. Using this resource, we find novel evidence of complex, regionally distinct hunter-gatherer and Eurasian admixture across sub-Saharan Africa. We identify new loci under selection, including loci related to malaria susceptibility and hypertension. We show that modern imputation panels (sets of reference genotypes from which unobserved or missing genotypes in study sets can be inferred) can identify association signals at highly differentiated loci across populations in sub-Saharan Africa. Using whole-genome sequencing, we demonstrate further improvements in imputation accuracy, strengthening the case for large-scale sequencing efforts of diverse African haplotypes. Finally, we present an efficient genotype array design capturing common genetic variation in Africa.