Journal article
Rare variants analyses suggest novel cleft genes in the African population
Scientific reports, Vol.14(1), 14279
06/20/2024
DOI: 10.1038/s41598-024-65151-9
PMCID: PMC11189897
PMID: 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.
Details
- Title: Subtitle
- Rare variants analyses suggest novel cleft genes in the African population
- Creators
- Azeez Alade - University of IowaPeter Mossey - University of DundeeWaheed Awotoye - University of IowaTamara Busch - University of IowaAbimbola M Oladayo - University of IowaEmmanuel Aladenika - University of IowaMojisola Olujitan - University of IowaEmma WentworthDeepti Anand - University of DelawareThirona Naicker - University of KwaZulu-NatalLord J. J Gowans - Kwame Nkrumah University of Science and TechnologyMekonen A Eshete - Addis Ababa UniversityWasiu L Adeyemo - University of LagosErliang Zeng - University of IowaEric Van Otterloo - University of IowaMichael O’Rorke - University of Iowa, EpidemiologyAdebowale Adeyemo - National Human Genome Research InstituteJeffrey C Murray - University of IowaJustin Cotney - University of ConnecticutSalil A Lachke - University of DelawarePaul Romitti - University of IowaAzeez Butali - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Scientific reports, Vol.14(1), 14279
- DOI
- 10.1038/s41598-024-65151-9
- PMID
- 38902479
- PMCID
- PMC11189897
- NLM abbreviation
- Sci Rep
- ISSN
- 2045-2322
- eISSN
- 2045-2322
- Publisher
- Nature Publishing Group
- Language
- English
- Date published
- 06/20/2024
- Academic Unit
- Preventive and Community Dentistry; Oral Pathology, Radiology and Medicine; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pathology; Iowa Neuroscience Institute; Biostatistics; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research; Periodontics
- Record Identifier
- 9984643757202771
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