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Cited by 139Forensic and Genetic ResearchGenetic Associations and EpidemiologyGenetic diversity and population structure

Patterns of Ancestry, Signatures of Natural Selection, and Genetic Association with Stature in Western African Pygmies

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Jarvis, Joseph P., Scheinfeldt, Laura B., Soi, Sameer, Lambert, Charla, Omberg, Larsson, Ferwerda, Bart, Froment, Alain, Bodo, Jean-Marie +4 more·2012·PLoS Genetics
DOI 10.1371/journal.pgen.1002641PMC PMC3343053
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Abstract

African Pygmy groups show a distinctive pattern of phenotypic variation, including short stature, which is thought to reflect past adaptation to a tropical environment. Here, we analyze Illumina 1M SNP array data in three Western Pygmy populations from Cameroon and three neighboring Bantu-speaking agricultural populations with whom they have admixed. We infer genome-wide ancestry, scan for signals of positive selection, and perform targeted genetic association with measured height variation. We identify multiple regions throughout the genome that may have played a role in adaptive evolution, many of which contain loci with roles in growth hormone, insulin, and insulin-like growth factor signaling pathways, as well as immunity and neuroendocrine signaling involved in reproduction and metabolism. The most striking results are found on chromosome 3, which harbors a cluster of selection and association signals between approximately 45 and 60 Mb. This region also includes the positional candidate genes DOCK3, which is known to be associated with height variation in Europeans, and CISH, a negative regulator of cytokine signaling known to inhibit growth hormone-stimulated STAT5 signaling. Finally, pathway analysis for genes near the strongest signals of association with height indicates enrichment for loci involved in insulin and insulin-like growth factor signaling.

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  • The Pygmy/non-Pygmy stature gap can be traced in part to specific differences in immune and neuroendocrine functioning.

    “Several authors (see, e.g., [33][34][35][36]) have applied these techniques to Pygmies, finding that the Pygmy/non-Pygmy stature gap can be traced in part to specific differences in immune and neuroendocrine functioning.”

    From Global Ancestry and Cognitive Ability (2019) · cites this paper as [33]

    The Results (Pathway Enrichment Analysis) find enrichment of neuroendocrine-signaling genes, and the Discussion (Conclusions and Future Studies) proposes a possible connection among immunity, neuroendocrine pathways, and short stature. Neither passage establishes specific differences in immune and neuroendocrine functioning as a demonstrated cause of the Pygmy/non-Pygmy stature gap; the paper presents candidate pathways and a hypothesis. (LLM, conf=0.86)

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Authors
Jarvis, J. P., Scheinfeldt, L. B., Soi, S., Lambert, C., Omberg, L., Ferwerda, B., Froment, A., Bodo, J.-M., Beggs, W., Hoffman, G., Mezey, J., & Tishkoff, S. A.
Affiliations
  • University of Pennsylvania (US)
  • Cornell University (US)
  • Muséum national d'Histoire naturelle (FR)
  • Ministry of Scientific Research and Innovation (CM)
Corresponding author
Tishkoff, Sarah A.
ORCID
Venue
PLoS Genetics
Publisher
Public Library of Science (PLoS)
Published
2012-04-26
Volume
8
Issue
4
Pages
e1002641
ISSN
  • 1553-7390 (ISSN-L)
  • 1553-7404
DOI
10.1371/journal.pgen.1002641
PMC
PMC3343053
OpenAlex
W1999771068
Cited by
139
References
10
Citations by year
2026: 2 · 2025: 2 · 2024: 7 · 2023: 4 · 2022: 7 · 2021: 14 · 2020: 12 · 2019: 10 · 2018: 8 · 2017: 10 · 2016: 13 · 2015: 12 · 2014: 15 · 2013: 17 · 2012: 6
FWCI
9.64
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS Genetics (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (publishedVersion, other-oa)
  • Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • National Science Foundation (0196183, 0922432, 1026555, 0827436)
  • Children's Hospital of Philadelphia
  • National Institutes of Health (DP1OD006445, DP1-OD-006445-01)
  • Weill Cornell Medical College
  • National Institute of Mental Health (P50MH079513)
  • National Human Genome Research Institute (1F32HG005290-01)
  • National Institute of General Medical Sciences (R01GM083606, R01GM076637)
  • National Institute of Environmental Health Sciences (DP1ES022577)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic diversity and population structure
Keywords
short stature, African pygmies, genetic ancestry, positive selection, adaptive evolution, growth hormone signaling, insulin signaling, insulin-like growth factor signaling, CISH, chromosome 3, immune signaling, neuroendocrine signaling
MeSH terms
Adaptation, Biological, Africa, Western, Body Height, Chromosome Mapping, Dwarfism, Ethnicity, Biological Evolution, Humans, Insulin-Like Growth Factor I, Nerve Tissue Proteins, Selection, Genetic, Growth Hormone, Genome, Human, Polymorphism, Single Nucleotide, Guanine Nucleotide Exchange Factors, Black People, Suppressor of Cytokine Signaling Proteins, Genetic Association Studies

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