Identification of 16q21 as a modifier of nonsyndromic orofacial cleft phenotypes.
Genet Epidemiol
; 41(8): 887-897, 2017 12.
Article
en En
| MEDLINE
| ID: mdl-29124805
ABSTRACT
Orofacial clefts (OFCs) are common, complex birth defects with extremely heterogeneous phenotypic presentations. Two common subtypes-cleft lip alone (CL) and CL plus cleft palate (CLP)-are typically grouped into a single phenotype for genetic analysis (i.e., CL with or without cleft palate, CL/P). However, mounting evidence suggests there may be unique underlying pathophysiology and/or genetic modifiers influencing expression of these two phenotypes. To this end, we performed a genome-wide scan for genetic modifiers by directly comparing 450 CL cases with 1,692 CLP cases from 18 recruitment sites across 13 countries from North America, Central or South America, Asia, Europe, and Africa. We identified a region on 16q21 that is strongly associated with different cleft type (P = 5.611 × 10-8 ). We also identified significant evidence of gene-gene interactions between this modifier locus and two recognized CL/P risk loci 8q21 and 9q22 (FOXE1) (P = 0.012 and 0.023, respectively). Single nucleotide polymorphism (SNPs) in the 16q21 modifier locus demonstrated significant association with CL over CLP. The marker alleles on 16q21 that increased risk for CL were found at highest frequencies among individuals with a family history of CL (P = 0.003). Our results demonstrate the existence of modifiers for which type of OFC develops and suggest plausible elements responsible for phenotypic heterogeneity, further elucidating the complex genetic architecture of OFCs.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Cromosomas Humanos Par 16
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Encéfalo
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Labio Leporino
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Fisura del Paladar
Tipo de estudio:
Diagnostic_studies
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Etiology_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Female
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Humans
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Male
Idioma:
En
Revista:
Genet Epidemiol
Asunto de la revista:
EPIDEMIOLOGIA
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GENETICA MEDICA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos