Five Priorities of African Genomics Research: The Next Frontier

Abstract

To embrace the prospects of accurately diagnosing thousands of monogenic conditions, predicting disease risks for complex traits or diseases, tailoring treatment to individuals’ pharmacogenetic profiles, and potentially curing some diseases, research into African genomic variation is a scientific imperative. African genomes harbor millions of uncaptured variants accumulated over 300,000 years of modern humans’ evolutionary history, with successive waves of admixture, migration, and natural selection combining with extensive ecological diversity to create a broad and exceptional genomic complexity. Harnessing African genomic complexity, therefore, will require sustained commitment and equitable collaboration from the scientific community and funding agencies. African governments must support academic public research and industrial partnerships that build the necessary genetic medicine workforce, utilize the emerging genomic big data to develop expertise in computer science and bioinformatics, and evolve national and global governance frameworks that recognize the ethical implications of data-driven genomic research and empower its application in African social, cultural, economic, and religious contexts. Expected final online publication date for the Annual Review of Genomics and Human Genetics, Volume 23 is October 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Leveraging our common African origins to understand human evolution and health

“…The deep evolutionary tree within Africa, with more time for recombination to separate linked alleles, combined with complex patterns of admixture across the continent creates highly heterogeneous haplotypes with limited linkage disequilibrium. 2 As further illustrated by the present paper, on average, a genome of African ancestry carries three to five times more variants than those from other ancestries. 7 In concert, there is a similar imperative to develop faster and better methods of accounting for admixture in the context of natural selection by teasing apart local ancestry, i.e., the likely ancestral parental haplotypes at a locus.…”

“…It is now clear that the detailed study of African genomic variation is a scientific imperative. 2 Therefore, the research reported from Fan et al. adds much needed data to our knowledge of African genomes and the information they contain about humanity’s history within Africa.…”

“…Quintessential examples include (1) variants in the β-globin gene ( HBB ) that cause sickle cell disease but confer resistance to malaria, (2) variants in APOL1 that are protective against trypanosomes but increase susceptibility to chronic kidney disease, (3) variants of OSBPL10 and RXRA that protect against dengue fever, and (4) variants in genes that play a role in lactose tolerance. 2 Another example is the Duffy allele ACKR1 _rs2814778-C, whose global map reflects adaptation to malaria, with a high frequency of the Duffy-null genotype in sub-Saharan Africa (>90%) and up to 65% among African Americans (who are primarily African-European admixed). A recent study showed that decisions on safety and discontinuation of azathioprine (a cancer medication) made upon deviations of neutrophil count values defined as “normal” in Europeans (absolute neutrophil count < 1.5 × 10 9 cells/L) can be inappropriate for Africans.…”

Immunogenetics and pharmacogenetics of allergic asthma in Africa

“…Genetic heterogeneity in African ancestry is also caused by fewer genetic population bottlenecks and the fact that human evolution began in Africa. This translated to much lower linkage disequilibrium and heterogenous haplotypes due to less genetic recombination ( 53 ). All these factors need to be considered in multi-ancestry analysis of genetic variations in disease and more so in complex diseases such as asthma which are driven by common variants with small effect sizes.…”

“Black Lives Matter and Black Research Matters”: the African Society of Human Genetics’ call to halt racism in science

“…Such data sharing should go hand in hand with plans to promote benefits to participating communities (Ramsay, 2022). Moreover, commercialization of geneomic research products needs appropriate regulation now more than ever as African genomes are likely to become central to major health-related discoveries (Wonkam et al, 2022). Hastiness to once more exploit this unique resource has contributed to legal challenges for an "African" Genome-Wide Association Studies (GWAS) DNA chip that was developed by a company that lacked sufficient engagement with key stakeholders (Stokstad, 2019).…”