Evaluating the promise of inclusion of African ancestry populations in genomics

Abstract

The lack of representation of diverse ancestral backgrounds in genomic research is well-known, and the resultant scientific and ethical limitations are becoming increasingly appreciated. The paucity of data on individuals with African ancestry is especially noteworthy as Africa is the birthplace of modern humans and harbors the greatest genetic diversity. It is expected that greater representation of those with African ancestry in genomic research will bring novel insights into human biology, and lead to improvements in clinical care and improved understanding of health disparities. Now that major efforts have been undertaken to address this failing, is there evidence of these anticipated advances? Here, we evaluate the promise of including diverse individuals in genomic research in the context of recent literature on individuals of African ancestry. In addition, we discuss progress and achievements on related technological challenges and diversity among scientists conducting genomic research.

Inclusion of Variants Discovered from Diverse Populations Improves Polygenic Risk Score Transferability

“…GWAS arrays and their imputation have substantially higher coverage among Europeans, and this may result in decreased PRS portability of findings across traits; in such situations, whole genome sequencing in diverse populations may be needed in order to improve accuracy21,22 . Our study and others support the immense genetic diversity that can be unlocked by studying underrepresented populations to both eliminate the disparity in genetics for prediction medicine and provide novel insights into disease biology for all populations19,21,23 .Although our simulation study provides important insight into the future of PRS use, it has important limitations. First, while coalescent simulations allow for decreased computational burden, model assumptions may result in inaccurate long-range linkage disequilibrium especially for whole genome simulations24 .…”

Strategic vision for improving human health at The Forefront of Genomics

“…Prioritizing the generation of genomic and corresponding phenotypic data from ancestrally diverse participants is a scientific imperative 104 and essential for achieving equitable benefits from genomic advances 105 (Box 1). However, this is an area in which genomics has repeatedly fallen short 19 , leading to missed opportunities for understanding genome structure and function, identifying variants conferring risk for common diseases 106 , and implementing genomic medicine for the benefit of all [107][108][109] .…”

Missing in Action: African Ancestry Brain Research

“…Homozygotes for the risk haplotype are three times less likely to be at risk of LOAD as are individuals of European ancestry with the same haplotype, despite AD being potentially twice as common in AA people ( Rajabli et al., 2018 ). Overall, individuals of AA have the most diverse genotypes and phenotypes of any population ( Bentley et al., 2020 ).…”

“…Polygene risk scores, which are based on summing risk-associated alleles at SNPs across the genomes from these GWAS datasets, predict illness risk in individuals of AA, on average, only one-fifth as strongly as predictions in people of European ancestry ( Martin et al., 2019 ). The inclusion of primarily European ancestry individuals in current genetic research limits understanding of how genetics influences disease ( Bentley et al., 2020 ) and obscures a significant portion of the potential for scientific advancements for personalizing medicine because emerging therapeutics may fail to apply equally to individuals of AA.…”