Journal article
Genome-wide association study of multiethnic nonsyndromic orofacial cleft families identifies novel loci specific to family and phenotypic subtypes
Genetic epidemiology, Vol.46(3-4), pp.182-198
04/2022
DOI: 10.1002/gepi.22447
PMCID: PMC9086172
PMID: 35191549
Abstract
Nonsyndromic orofacial clefts (OFCs) are among the most common craniofacial birth defects worldwide, and known to exhibit phenotypic and genetic heterogeneity. Cleft lip plus cleft palate (CLP) and cleft lip only (CL) are commonly combined together as one phenotype (CL/P), separately from cleft palate alone. In comparison, our study analyzes CL and CLP separately. A sample of 2218 CL and CLP cases, 4537 unaffected relatives of cases, and 2673 pure controls with no family history of OFC were selected from the Pittsburgh Orofacial Cleft (Pitt-OFC) multiethnic study.genome-wide association studies were run for seven specific phenotypes created based on the cleft type(s) observed within these families, as well as the combined CL/P phenotype. Five novel genome-wide significant associations, 3q29 (rs62284390), 5p13.2 (rs609659), 7q22.1 (rs6465810), 19p13.3 (rs628271), and 20q13.33 (rs2427238), and nine associations (p ≤ 1.0E-05) within previously confirmed OFC loci-PAX7, IRF6, FAM49A, DCAF4L2, 8q24.21, ARID3B, NTN1, TANC2 and the WNT9B:WNT3 gene cluster-were observed. We also found that single nucleotide polymorphisms within a subset of the associated loci, both previously known and novel, differ substantially in terms of their effects across cleft- or family-specific phenotypes, indicating not only etiologic differences between CL and CLP, but also genetic heterogeneity within each of the two OFC subtypes.
Details
- Title: Subtitle
- Genome-wide association study of multiethnic nonsyndromic orofacial cleft families identifies novel loci specific to family and phenotypic subtypes
- Creators
- Nandita Mukhopadhyay - University of PittsburghEleanor Feingold - University of PittsburghLina Moreno-Uribe - University of IowaGeorge Wehby - University of IowaLuz Consuelo Valencia-Ramirez - Fundación Clínica Noel, Antioquia, Colombia.Claudia P Restrepo Muñeton - Fundación Clínica Noel, Antioquia, ColombiaCarmencita Padilla - University of the Philippines ManilaFrederic Deleyiannis - University of Colorado HealthKaare Christensen - University of Southern DenmarkFernando A Poletta - CEMIC-CONICET: Center for Medical Education and Clinical Research, Buenos Aires, Argentina.Ieda M Orioli - Universidade Federal do Rio de JaneiroJacqueline T Hecht - The University of Texas Health Science Center at HoustonCarmen J Buxó - University of Puerto Rico SystemAzeez Butali - University of IowaWasiu L Adeyemo - University of LagosAlexandre R Vieira - University of PittsburghJohn R Shaffer - University of PittsburghJeffrey C Murray - University of IowaSeth M Weinberg - University of PittsburghElizabeth J Leslie - Emory UniversityMary L Marazita - University of Pittsburgh
- Resource Type
- Journal article
- Publication Details
- Genetic epidemiology, Vol.46(3-4), pp.182-198
- DOI
- 10.1002/gepi.22447
- PMID
- 35191549
- PMCID
- PMC9086172
- NLM abbreviation
- Genet Epidemiol
- ISSN
- 0741-0395
- eISSN
- 1098-2272
- Grant note
- R01-DE011931 / NIH National Institute of Dental and Craniofacial Research R01 DE016148 / NIDCR NIH HHS U01-DE024425 / NIH National Institute of Dental and Craniofacial Research K99/R00DE024571 / NIH National Institute of Dental and Craniofacial Research R01-DE28300 / NIH National Institute of Dental and Craniofacial Research U54GM133807 / NIH National Institute of General Medical Sciences R01 DE014667 / NIDCR NIH HHS R01-DE014667 / NIH National Institute of Dental and Craniofacial Research R37-DE-008559 / NIH National Institute of Dental and Craniofacial Research HHSN268201200008I / NHLBI NIH HHS R01-DE012472 / NIH National Institute of Dental and Craniofacial Research R01 DE028300 / NIDCR NIH HHS Institute of Human Genetics, National Institutes of Health, University of the Philippines, Manila, grants through FAPERJ HHSN268201200008C / NHLBI NIH HHS R01 DE009886 / NIDCR NIH HHS S21 MD001830 / NIMHD NIH HHS R01-DE-016148 / NIH National Institute of Dental and Craniofacial Research S21MD001830 / NIMHD NIH HHS R01 DE028342 / NIDCR NIH HHS U54 GM133807 / NIGMS NIH HHS R01 DD000295 / NCBDD CDC HHS R01-DE009886 / NIH National Institute of Dental and Craniofacial Research R21 DE016930 / NIDCR NIH HHS R21-DE016930 / NIH National Institute of Dental and Craniofacial Research R01-DE028342 / NIH National Institute of Dental and Craniofacial Research X01-HG007485 / NIH National Human Genome Research Institute R00 DE024571 / NIDCR NIH HHS R37 DE008559 / NIDCR NIH HHS U01-DD000295 / NIH National Institute of Dental and Craniofacial Research R00 DE025060 / NIDCR NIH HHS R00-DE025060 / NIH National Institute of Dental and Craniofacial Research Research Institute of the Children's Hospital of Colorado U01 DE024425 / NIDCR NIH HHS R01 DE011931 / NIDCR NIH HHS
- Language
- English
- Date published
- 04/2022
- Academic Unit
- Preventive and Community Dentistry; Orthodontics; Oral Pathology, Radiology and Medicine; Anatomy and Cell Biology; Health Management and Policy; Stead Family Department of Pediatrics; Epidemiology; Economics; Pediatric Dentistry; Craniofacial Anomalies Research Center; Public Policy Center (Archive); Dental Research
- Record Identifier
- 9984353926802771
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