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The Critical Needs and Challenges for Genetic Architecture Studies in Africa

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Martin, Alicia R, Teferra, Solomon, Möller, Marlo, Hoal, Eileen G, Daly, Mark J·2018·Current Opinion in Genetics & Development
DOI 10.1016/j.gde.2018.08.005PMC PMC6494470
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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.

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  • Africa retains the most genetic diversity, and Africans are understudied but disproportionately informative for genetic analyses and evolutionary history.

    “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 history27,73.”

    From Clinical use of current polygenic risk scores may exacerbate health disparities (2019) · cites this paper as [73]

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Authors
Martin, A. R., Teferra, S., Möller, M., Hoal, E. G., & Daly, M. J.
Affiliations
  • Broad Institute (US)
  • Harvard University (US)
  • South African Medical Research Council (ZA)
Corresponding author
Martin, Alicia R
ORCID
Venue
Current Opinion in Genetics & Development
Publisher
Elsevier BV
Published
2018-12
Volume
53
Pages
113-120
ISSN
0959-437X (ISSN-L)
DOI
10.1016/j.gde.2018.08.005
PMC
PMC6494470
OpenAlex
W2808421411
Cited by
76
References
12
Citations by year
2026: 3 · 2025: 11 · 2024: 8 · 2023: 10 · 2022: 10 · 2021: 11 · 2020: 15 · 2019: 6 · 2018: 1 · 2017: 1
FWCI
1.16
Type
journal article
Language
en
Open access
Licence
Locations
  • Current Opinion in Genetics & Development (acceptedVersion)
  • Preprints.org (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Työväentutkimus Vuosikirja (submittedVersion, other-oa)
Funders
NIH (K99MH117229)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Race, Genetics, and Society
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
Keywords
genetic architecture, African populations, population genetic variation, complex traits, disease genetics, fine mapping, genetic risk prediction, research capacity building
MeSH terms
Africa, Genetics, Population, Humans, Genome, Human, Polymorphism, Single Nucleotide, Genomics, Black People, Genome-Wide Association Study

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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