Genome scans of facial features in East Africans and cross-population comparisons reveal novel associations.
Journal
PLoS genetics
ISSN: 1553-7404
Titre abrégé: PLoS Genet
Pays: United States
ID NLM: 101239074
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
14
11
2020
accepted:
02
07
2021
entrez:
19
8
2021
pubmed:
20
8
2021
medline:
19
11
2021
Statut:
epublish
Résumé
Facial morphology is highly variable, both within and among human populations, and a sizable portion of this variation is attributable to genetics. Previous genome scans have revealed more than 100 genetic loci associated with different aspects of normal-range facial variation. Most of these loci have been detected in Europeans, with few studies focusing on other ancestral groups. Consequently, the degree to which facial traits share a common genetic basis across diverse sets of humans remains largely unknown. We therefore investigated the genetic basis of facial morphology in an East African cohort. We applied an open-ended data-driven phenotyping approach to a sample of 2,595 3D facial images collected on Tanzanian children. This approach segments the face into hierarchically arranged, multivariate features that capture the shape variation after adjusting for age, sex, height, weight, facial size and population stratification. Genome scans of these multivariate shape phenotypes revealed significant (p < 2.5 × 10-8) signals at 20 loci, which were enriched for active chromatin elements in human cranial neural crest cells and embryonic craniofacial tissue, consistent with an early developmental origin of the facial variation. Two of these associations were in highly conserved regions showing craniofacial-specific enhancer activity during embryological development (5q31.1 and 12q21.31). Six of the 20 loci surpassed a stricter threshold accounting for multiple phenotypes with study-wide significance (p < 6.25 × 10-10). Cross-population comparisons indicated 10 association signals were shared with Europeans (seven sharing the same associated SNP), and facilitated fine-mapping of causal variants at previously reported loci. Taken together, these results may point to both shared and population-specific components to the genetic architecture of facial variation.
Identifiants
pubmed: 34411106
doi: 10.1371/journal.pgen.1009695
pii: PGENETICS-D-20-01742
pmc: PMC8375984
doi:
Types de publication
Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1009695Subventions
Organisme : Wellcome Trust
ID : 217065/Z/19/Z
Pays : United Kingdom
Organisme : NIDCR NIH HHS
ID : R01 DE027023
Pays : United States
Organisme : NIDCR NIH HHS
ID : U01 DE020054
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE016148
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201200008I
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NIDCR NIH HHS
ID : U01 DE020078
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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