Integrative approaches generate insights into the architecture of non-syndromic cleft lip with or without cleft palate.
GWAS
chromatin mark
cleft
craniofacial development
regulatory effects
Journal
HGG advances
ISSN: 2666-2477
Titre abrégé: HGG Adv
Pays: United States
ID NLM: 101772885
Informations de publication
Date de publication:
08 Jul 2021
08 Jul 2021
Historique:
received:
19
01
2021
accepted:
27
05
2021
entrez:
20
1
2022
pubmed:
21
1
2022
medline:
21
1
2022
Statut:
epublish
Résumé
Non-syndromic cleft lip with or without cleft palate (nsCL/P) is a common congenital facial malformation with a multifactorial etiology. Genome-wide association studies (GWASs) have identified multiple genetic risk loci. However, functional interpretation of these loci is hampered by the underrepresentation in public resources of systematic functional maps representative of human embryonic facial development. To generate novel insights into the etiology of nsCL/P, we leveraged published GWAS data on nsCL/P as well as available chromatin modification and expression data on mid-facial development. Our analyses identified five novel risk loci, prioritized candidate target genes within associated regions, and highlighted distinct pathways. Furthermore, the results suggest the presence of distinct regulatory effects of nsCL/P risk variants throughout mid-facial development and shed light on its regulatory architecture. Our integrated data provide a platform to advance hypothesis-driven molecular investigations of nsCL/P and other human facial defects.
Identifiants
pubmed: 35047836
doi: 10.1016/j.xhgg.2021.100038
pii: S2666-2477(21)00019-1
pmc: PMC8756534
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100038Subventions
Organisme : NIDCR NIH HHS
ID : R00 DE025060
Pays : United States
Organisme : NIDCR NIH HHS
ID : R03 DE027103
Pays : United States
Informations de copyright
© 2021 The Authors.
Déclaration de conflit d'intérêts
The authors declare no competing interests.
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