The critical needs and challenges for genetic architecture studies in Africa

Abstract

Human genetic studies have long been vastly Eurocentric, raising a key question about the generalizability of these study findings to other populations. Because humans originated in Africa, these populations retain more genetic diversity, and yet individuals of African descent have been tremendously underrepresented in genetic studies. The diversity in Africa affords ample opportunities to improve fine-mapping resolution for associated loci, discover novel genetic associations with phenotypes, build more generalizable genetic risk prediction models, and better understand the genetic architecture of complex traits and diseases subject to varying environmental pressures. Thus, it is both ethically and scientifically imperative that geneticists globally surmount challenges that have limited progress in African genetic studies to date. Additionally, African investigators need to be meaningfully included, as greater inclusivity and enhanced research capacity afford enormous opportunities to accelerate genomic discoveries that translate more effectively to all populations. We review the advantages, challenges, and examples of genetic architecture studies of complex traits and diseases in Africa. For example, with greater genetic diversity comes greater ancestral heterogeneity; this higher level of understudied diversity can yield novel genetic findings, but some methods that assume homogeneous population structure and work well in European populations may work less well in the presence of greater heterogeneity in African populations. Consequently, we advocate for methodological development that will accelerate studies important for all populations, especially those currently underrepresented in genetics.

Current clinical use of polygenic scores will risk exacerbating health disparities

“…Notably, some of these biobanks such as UK Biobank have participants with considerable global genetic diversity that enables multi-ethnic comparisons; although minorities from this cohort provide the largest deeply phenotyped GWAS cohorts for several ancestries, these individuals are often excluded in current statistical analyses in favor of single ancestries, large sample sizes, and the simplicity afforded by genetic homogeneity. These considerations notwithstanding, there are critical needs and challenges for expanding the scale of genetic studies of heritable traits in diverse populations; this is especially apparent in Africa where humans originated and retain the most genetic diversity, as Africans are understudied but disproportionately informative for genetic analyses and evolutionary history 27,73 . The most notable investment here comes from the Human Heredity and Health in Africa (H3Africa) Initiative, increasing genomics research capacity in Africa through more than $216 million in funding from the NIH (USA) and Wellcome Trust (UK) for genetics research led by African investigators 56,74 .…”

The Emergence of Genomic Research in Africa and New Frameworks for Equity in Biomedical Research

“…3) necessary laboratory equipment to conduct assays; and 4) the infrastructure to maintain that equipment, each of which may be challenging in the African context. 3,27 To achieve improvements in equitable collaborations, research capacity must be enhanced. The Framework for African Genomics and Biobanking recommends that sample export be accompanied by measures to improve the research capabilities of the region in which samples were collected and where there is a demonstrated focus on reducing global health inequality.…”

“…-Bentley et al in Africa, 8 and studying only the genetic variation that exists outside of Africa curtails the potential insights that can come from genetic associations. 3 Within Africa may lie new discoveries for human biology and opportunities for a more complete mapping of human history. 2 Such discoveries are already being reported, as the inclusion of understudied African populations Beyond these reasons for including Africans in genomic research, there are also important reasons for inclusion related to equity for individuals with African ancestry.…”

Novel and Known Gene-Smoking Interactions With cIMT Identified as Potential Drivers for Atherosclerosis Risk in West-African Populations of the AWI-Gen Study

“…A previous study reported that African populations were more diverse and had significantly more genes and pathways involved in extreme allele frequency differences (EAFD) (Sulovari et al, 2017). The African genome is therefore highly relevant for the discovery of new genetic associations and a better understanding of human disease mechanisms (Tekola-Ayele and Rotimi, 2015;Choudhury et al, 2018;Martin et al, 2018).…”