Journal article
Shared genetic risk between major orofacial cleft phenotypes in an African population
Genetic epidemiology, Vol.48(6), pp.258-269
08/26/2024
DOI: 10.1002/gepi.22564
PMID: 38634654
Appears in UI Libraries Support Open Access
Abstract
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.
Details
- Title: Subtitle
- Shared genetic risk between major orofacial cleft phenotypes in an African population
- Creators
- Azeez Alade - Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa, USATabitha Peter - University of IowaTamara Busch - University of IowaWaheed Awotoye - University of IowaDeepti Anand - University of DelawareOladayo Abimbola - Iowa Institute of Oral Health Research, University of Iowa, Iowa City, Iowa, USAEmmanuel Aladenika - University of IowaMojisola Olujitan - University of IowaOscar Rysavy - Iowa Institute of Oral Health Research, University of Iowa, Iowa City, Iowa, USAPhuong Fawng Nguyen - Iowa Institute of Oral Health Research, University of Iowa, Iowa City, Iowa, USAThirona Naicker - University of KwaZulu-NatalPeter A Mossey - University of DundeeLord 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 IowaAdebowale Adeyemo - National Human Genome Research InstituteJeffrey C Murray - University of IowaSalil A Lachke - University of DelawarePaul A Romitti - University of IowaAzeez Butali - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Genetic epidemiology, Vol.48(6), pp.258-269
- DOI
- 10.1002/gepi.22564
- PMID
- 38634654
- NLM abbreviation
- Genet Epidemiol
- ISSN
- 0741-0395
- eISSN
- 1098-2272
- Publisher
- Wiley
- Grant note
- NIDCR NIH HHS
- Language
- English
- Electronic publication date
- 04/18/2024
- Date published
- 08/26/2024
- 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
- 9984616957302771
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