Rare variants analyses suggest novel cleft genes in the African population.
Sci Rep
; 14(1): 14279, 2024 06 20.
Article
en En
| MEDLINE
| ID: mdl-38902479
ABSTRACT
Non-syndromic orofacial clefts (NSOFCs) are common birth defects with a complex etiology. While over 60 common risk loci have been identified, they explain only a small proportion of the heritability for NSOFCs. Rare variants have been implicated in the missing heritability. Thus, our study aimed to identify genes enriched with nonsynonymous rare coding variants associated with NSOFCs. Our sample included 814 non-syndromic cleft lip with or without palate (NSCL/P), 205 non-syndromic cleft palate only (NSCPO), and 2150 unrelated control children from Nigeria, Ghana, and Ethiopia. We conducted a gene-based analysis separately for each phenotype using three rare-variants collapsing models (1) protein-altering (PA), (2) missense variants only (MO); and (3) loss of function variants only (LOFO). Subsequently, we utilized relevant transcriptomics data to evaluate associated gene expression and examined their mutation constraint using the gnomeAD database. In total, 13 genes showed suggestive associations (p = E-04). Among them, eight genes (ABCB1, ALKBH8, CENPF, CSAD, EXPH5, PDZD8, SLC16A9, and TTC28) were consistently expressed in relevant mouse and human craniofacial tissues during the formation of the face, and three genes (ABCB1, TTC28, and PDZD8) showed statistically significant mutation constraint. These findings underscore the role of rare variants in identifying candidate genes for NSOFCs.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Labio Leporino
/
Fisura del Paladar
Límite:
Animals
/
Child
/
Female
/
Humans
/
Male
País/Región como asunto:
Africa
Idioma:
En
Revista:
Sci Rep
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos