title: Patterns of ancestry, signatures of natural selection, and genetic association with stature in Western African pygmies.
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.
authors.affiliation: Department of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Jarvis
authors.forename: Laura B
authors.initials: LB
authors.lastname: Scheinfeldt
authors.forename: Sameer
authors.initials: S
authors.lastname: Soi
authors.forename: Charla
authors.initials: C
authors.lastname: Lambert
authors.forename: Larsson
authors.initials: L
authors.lastname: Omberg
authors.forename: Bart
authors.initials: B
authors.lastname: Ferwerda
authors.forename: Alain
authors.initials: A
authors.lastname: Froment
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Bodo
authors.forename: William
authors.initials: W
authors.lastname: Beggs
authors.forename: Gabriel
authors.initials: G
authors.lastname: Hoffman
authors.forename: Jason
authors.initials: J
authors.lastname: Mezey
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Tishkoff
mesh_terms: D000220:Adaptation, Biological; D000354:Africa, Western; D005075:Biological Evolution; D044383:Black People; D001827:Body Height / Q000235:genetics*; D002874:Chromosome Mapping; D004392:Dwarfism / Q000235:genetics; D005006:Ethnicity / Q000235:genetics*; D056726:Genetic Association Studies; D015894:Genome, Human; D013006:Growth Hormone / Q000235:genetics; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics
chemical_list: D013006:Growth Hormone; D020662:Guanine Nucleotide Exchange Factors; D007334:Insulin-Like Growth Factor I; D009419:Nerve Tissue Proteins; D050826:Suppressor of Cytokine Signaling Proteins; C485840:DOCK3 protein, human