Journal article
Association Studies and Direct DNA Sequencing Implicate Genetic Susceptibility Loci in the Etiology of Nonsyndromic Orofacial Clefts in Sub-Saharan African Populations
Journal of dental research, Vol.95(11), pp.1245-1256
10/2016
DOI: 10.1177/0022034516657003
PMCID: PMC5076758
PMID: 27369588
Abstract
Orofacial clefts (OFCs) are congenital dysmorphologies of the human face and oral cavity, with a global incidence of 1 per 700 live births. These anomalies exhibit a multifactorial pattern of inheritance, with genetic and environmental factors both playing crucial roles. Many loci have been implicated in the etiology of nonsyndromic cleft lip with or without cleft palate (NSCL/P) in populations of Asian and European ancestries, through genome-wide association studies and candidate gene studies. However, few populations of African descent have been studied to date. Here, the authors show evidence of an association of some loci with NSCL/P and nonsyndromic cleft palate only (NSCPO) in cohorts from Africa (Ghana, Ethiopia, and Nigeria). The authors genotyped 48 single-nucleotide polymorphisms that were selected from previous genome-wide association studies and candidate gene studies. These markers were successfully genotyped on 701 NSCL/P and 163 NSCPO cases, 1,070 unaffected relatives, and 1,078 unrelated controls. The authors also directly sequenced 7 genes in 184 nonsyndromic OFC (NSOFC) cases and 96 controls from Ghana. Population-specific associations were observed in the case-control analyses of the subpopulations, with West African subpopulations (Ghana and Nigeria) showing a similar pattern of associations. In meta-analyses of the case-control cohort, PAX7 (rs742071, P = 5.10 × 10(-3)), 8q24 (rs987525, P = 1.22 × 10(-3)), and VAX1 (rs7078160, P = 0.04) were nominally associated with NSCL/P, and MSX1 (rs115200552, P = 0.01), TULP4 (rs651333, P = 0.04), CRISPLD2 (rs4783099, P = 0.02), and NOG1 (rs17760296, P = 0.04) were nominally associated with NSCPO. Moreover, 7 loci exhibited evidence of threshold overtransmission in NSOFC cases through the transmission disequilibrium test and through analyses of the family-based association for disease traits. Through DNA sequencing, the authors also identified 2 novel, rare, potentially pathogenic variants (p.Asn323Asp and p.Lys426IlefsTer6) in ARHGAP29 In conclusion, the authors have shown evidence for the association of many loci with NSCL/P and NSCPO. To the best of this knowledge, this study is the first to demonstrate any of these association signals in any African population.
Details
- Title: Subtitle
- Association Studies and Direct DNA Sequencing Implicate Genetic Susceptibility Loci in the Etiology of Nonsyndromic Orofacial Clefts in Sub-Saharan African Populations
- Creators
- L J J Gowans - Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana Cleft Clinic, Komfo Anokye Teaching Hospital, Kumasi, Ghana Department of Pediatrics, University of Iowa, Iowa City, IA, USA Department of Oral Pathology, Radiology and Medicine, University of Iowa, Iowa City, IA, USAW L Adeyemo - College of Medicine, University of Lagos, Lagos, NigeriaM Eshete - Addis Ababa University, Addis Ababa, EthiopiaP A Mossey - Department of Orthodontics, University of Dundee, Dundee, ScotlandT Busch - Department of Oral Pathology, Radiology and Medicine, University of Iowa, Iowa City, IA, USAB Aregbesola - Obafemi Awolowo University Teaching Hospital, Ile-Ife, NigeriaP Donkor - Cleft Clinic, Komfo Anokye Teaching Hospital, Kumasi, Ghana Department of Surgery, School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, GhanaF K N Arthur - Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology, Kumasi, GhanaS A Bello - Department of Oral and Maxillofacial Surgery, State House Hospital, Abuja, NigeriaA Martinez - Department of Oral Pathology, Radiology and Medicine, University of Iowa, Iowa City, IA, USAM Li - Department of Oral Pathology, Radiology and Medicine, University of Iowa, Iowa City, IA, USAE A Augustine-Akpan - Department of Oral Pathology, Radiology and Medicine, University of Iowa, Iowa City, IA, USAW Deressa - Addis Ababa University, Addis Ababa, EthiopiaP Twumasi - Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology, Kumasi, GhanaJ Olutayo - College of Medicine, University of Lagos, Lagos, NigeriaM Deribew - Addis Ababa University, Addis Ababa, EthiopiaP Agbenorku - Cleft Clinic, Komfo Anokye Teaching Hospital, Kumasi, Ghana Department of Surgery, School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, GhanaA A Oti - Cleft Clinic, Komfo Anokye Teaching Hospital, Kumasi, Ghana Department of Surgery, School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, GhanaR Braimah - Obafemi Awolowo University Teaching Hospital, Ile-Ife, NigeriaG Plange-Rhule - Cleft Clinic, Komfo Anokye Teaching Hospital, Kumasi, GhanaM Gesses - Yekatit 12 Hospital Medical College, Addis Ababa, EthiopiaS Obiri-Yeboah - Cleft Clinic, Komfo Anokye Teaching Hospital, Kumasi, Ghana Department of Surgery, School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, GhanaG O Oseni - Department of Burns and Plastic Surgery, Ladoke Akintola University of Technology Teaching Hospital, Osogbo, NigeriaP B Olaitan - Department of Burns and Plastic Surgery, Ladoke Akintola University of Technology Teaching Hospital, Osogbo, NigeriaL Abdur-Rahman - Division of Pediatric Surgery, Department of Surgery, University of Ilorin, Ilorin, NigeriaF Abate - Yekatit 12 Hospital Medical College, Addis Ababa, EthiopiaT Hailu - Yekatit 12 Hospital Medical College, Addis Ababa, EthiopiaP Gravem - Haukeland University Hospital Bergen, Bergen, NorwayM O Ogunlewe - Department of Burns and Plastic Surgery, Ladoke Akintola University of Technology Teaching Hospital, Osogbo, NigeriaC J Buxó - School of Dental Medicine, University of Puerto Rico Medical Science Campus, San Juan, Puerto RicoM L Marazita - Department of Oral Biology, University of Pittsburgh, Pittsburgh, PA, USAA A Adeyemo - Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USAJ C Murray - Department of Pediatrics, University of Iowa, Iowa City, IA, USAA Butali - Department of Oral Pathology, Radiology and Medicine, University of Iowa, Iowa City, IA, USA azeez-butali@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Journal of dental research, Vol.95(11), pp.1245-1256
- DOI
- 10.1177/0022034516657003
- PMID
- 27369588
- PMCID
- PMC5076758
- NLM abbreviation
- J Dent Res
- ISSN
- 0022-0345
- eISSN
- 1544-0591
- Publisher
- United States
- Grant note
- S21 MD001830 / NIMHD NIH HHS R25 MD007607 / NIMHD NIH HHS R00 DE022378 / NIDCR NIH HHS R01 DE016148 / NIDCR NIH HHS R37 DE008559 / NIDCR NIH HHS K99 DE024571 / NIDCR NIH HHS R01 DE009886 / NIDCR NIH HHS U54 MD007587 / NIMHD NIH HHS
- Language
- English
- Date published
- 10/2016
- Academic Unit
- Oral Pathology, Radiology and Medicine; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984025457002771
Metrics
18 Record Views