Shared genetic risk between major orofacial cleft phenotypes in an African population.
craniofacial
genetics
nonsyndromic
orofacial clefts
pleiotropy
single‐nucleotide variations
transcriptomics
Journal
Genetic epidemiology
ISSN: 1098-2272
Titre abrégé: Genet Epidemiol
Pays: United States
ID NLM: 8411723
Informations de publication
Date de publication:
18 Apr 2024
18 Apr 2024
Historique:
revised:
22
02
2024
received:
14
07
2023
accepted:
27
03
2024
medline:
18
4
2024
pubmed:
18
4
2024
entrez:
18
4
2024
Statut:
aheadofprint
Résumé
Nonsyndromic orofacial clefts (NSOFCs) represent a large proportion (70%-80%) of all OFCs. They can be broadly categorized into nonsyndromic cleft lip with or without cleft palate (NSCL/P) and nonsyndromic cleft palate only (NSCPO). Although NSCL/P and NSCPO are considered etiologically distinct, recent evidence suggests the presence of shared genetic risks. Thus, we investigated the genetic overlap between NSCL/P and NSCPO using African genome-wide association study (GWAS) data on NSOFCs. These data consist of 814 NSCL/P, 205 NSCPO cases, and 2159 unrelated controls. We generated common single-nucleotide variants (SNVs) association summary statistics separately for each phenotype (NSCL/P and NSCPO) under an additive genetic model. Subsequently, we employed the pleiotropic analysis under the composite null (PLACO) method to test for genetic overlap. Our analysis identified two loci with genome-wide significance (rs181737795 [p = 2.58E-08] and rs2221169 [p = 4.5E-08]) and one locus with marginal significance (rs187523265 [p = 5.22E-08]). Using mouse transcriptomics data and information from genetic phenotype databases, we identified MDN1, MAP3k7, KMT2A, ARCN1, and VADC2 as top candidate genes for the associated SNVs. These findings enhance our understanding of genetic variants associated with NSOFCs and identify potential candidate genes for further exploration.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIDCR NIH HHS
Pays : United States
Informations de copyright
© 2024 The Authors. Genetic Epidemiology published by Wiley Periodicals LLC.
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