Journal Article

The genetic and evolutionary basis of gene expression variation in East Africans

Rawlings-Goss, Renata A., Ranciaro, Alessia, Woldemeskel, Dawit, Ma, Rong, Brown, Christopher D., Beggs, William, Belay, Gurja, Yeager, Meredith, Nyambo, Thomas B., Kelly, Derek E., Li, Hongzhe, Grant, Gregory R., Hirbo, Jibril B., Ramdas, Shweta, Chanock, Stephen, Omar, Sabah A., Tishkoff, Sarah A.

2023

Overview

Background Mapping of quantitative trait loci (QTL) associated with molecular phenotypes is a powerful approach for identifying the genes and molecular mechanisms underlying human traits and diseases, though most studies have focused on individuals of European descent. While important progress has been made to study a greater diversity of human populations, many groups remain unstudied, particularly among indigenous populations within Africa. To better understand the genetics of gene regulation in East Africans, we perform expression and splicing QTL mapping in whole blood from a cohort of 162 diverse Africans from Ethiopia and Tanzania. We assess replication of these QTLs in cohorts of predominantly European ancestry and identify candidate genes under selection in human populations. Results We find the gene regulatory architecture of African and non-African populations is broadly shared, though there is a considerable amount of variation at individual loci across populations. Comparing our analyses to an equivalently sized cohort of European Americans, we find that QTL mapping in Africans improves the detection of expression QTLs and fine-mapping of causal variation. Integrating our QTL scans with signatures of natural selection, we find several genes related to immunity and metabolism that are highly differentiated between Africans and non-Africans, as well as a gene associated with pigmentation. Conclusion Extending QTL mapping studies beyond European ancestry, particularly to diverse indigenous populations, is vital for a complete understanding of the genetic architecture of human traits and can reveal novel functional variation underlying human traits and disease.

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: ancestry / Animal Genetics and Genomics / Bioinformatics / Biomedical and Life Sciences / blood / Chromosome Mapping / Datasets / East African People / eQTL / Ethiopia / Evolutionary Biology / Gene Expression / Gene mapping / Gene regulation / genes / Genetic diversity / Genetic Variation / Genomes / Genomics / Human African genomics / Human diversity / Human Genetics / Humans / immunity / Life Sciences / metabolism / Microbial Genetics and Genomics / Molecular modelling / Natural selection / Phenotypes / Pigmentation / Plant Genetics and Genomics / Quantitative Trait Loci / quantitative traits / Tanzania