Identifying the Genetic and Environmental Determinants of Gene Expression Variation in Africans

Gene regulation plays a predominant role in human evolution and complex traits, and high throughput methods are making the measurement of expression variation routine. However, studies to date have failed to capture the breadth of global genetic and environmental diversity by focusing primarily on Western individuals of European descent. Studies of Africans, who harbor the most genetic variation in the world and are exposed to a diversity of environmental variables and diets, are necessary to complete our understanding of how evolution has shaped human genetic and phenotypic diversity. To identify genetic and environmental contributors to gene expression variation in whole blood we have collected RNA sequencing data from 171 individuals representing 9 diverse African populations. Differential expression analyses uncover genes correlated with ancestry and environmental variables, clustering individuals by ancestry and diet. Combining expression data with SNP genotypes, we also map cis-eQTLs in our samples. The majority of identified eQTLs replicate in Europeans, though they can often be mapped to a more narrow credible set owing to the shorter tracks of linkage-disequilibrium in Africa. Conversely, those that fail to replicate are enriched for variants that are at moderate frequency in Africa and are low frequency or monomorphic in Europe. Using these eQTLs, allele frequency differentiation and scans of natural selection identify candidate genes and pathways that may have undergone positive selection in these populations. This study represents the most diverse study of gene expression in Africans to date and highlights the need to extend genomics studies to non-European populations.