Gene

Heritability

Demography

Whole genome sequencing

Biology

Imputation (statistics)

Demographic history

Trait

Computer science

Evolutionary biology

Single-nucleotide polymorphism

Genetics

Missing data

Genome

Genome-wide association study

Genotype

Population

Sociology

Programming language

Genetic variation

Machine learning

Cell

Genomic studies in African populations provide unique opportunities to understand disease etiology, human diversity, and population history. In the largest study of its kind, comprising genome-wide data from 6,400 individuals and whole-genome sequences from 1,978 individuals from rural Uganda, we find evidence of geographically correlated fine-scale population substructure. Historically, the ancestry of modern Ugandans was best represented by a mixture of ancient East African pastoralists. We demonstrate the value of the largest sequence panel from Africa to date as an imputation resource. Examining 34 cardiometabolic traits, we show systematic differences in trait heritability between European and African populations, probably reflecting the differential impact of genes and environment. In a multi-trait pan-African GWAS of up to 14,126 individuals, we identify novel loci associated with anthropometric, hematological, lipid, and glycemic traits. We find that several functionally important signals are driven by Africa-specific variants, highlighting the value of studying diverse populations across the region.

Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa