The genetic and evolutionary basis of gene expression variation in East Africans.
Loading...
Date
2023-02-24
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Genome Biology
Abstract
Background:
Mapping of quantitative trait loci (QTL) associated with molecular phe‑
notypes is a powerful approach for identifying the genes and molecular mechanisms
underlying human traits and diseases, though most studies have focused on individu‑
als 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 popula‑
tions 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 metabo‑
lism 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.
Description
Keywords
Human African genomics, Gene expression, Human diversity
Citation
Kelly, D.E., Ramdas, S., Ma, R., Rawlings-Goss, R.A., Grant, G.R., Ranciaro, A., Hirbo, J.B., Beggs, W., Yeager, M., Chanock, S. and Nyambo, T.B., 2023. The genetic and evolutionary basis of gene expression variation in East Africans. Genome Biology, 24(1), pp.1-24.