Artículo
Identification of 16q21 as a modifier of nonsyndromic orofacial cleft phenotypes
Carlson, Jenna C.; Standley, Jennifer; Petrin, Aline; Shaffer, John R.; Butali, Azeez; Buxó, Carmen J.; Castilla, Eduardo Enrique
; Christensen, Kaare; Deleyiannis, Frederic W.-D.; Hecht, Jacqueline T.; Field, L. Leigh; Garidkhuu, Ariuntuul; Moreno Uribe, Lina M.; Nagato, Natsume; Orioli, Ieda M.; Padilla, Carmencita; Poletta, Fernando Adrián
; Suzuki, Satoshi; Vieira, Alexandre R.; Wehby, George; Weinberg, Seth M.; Beaty, Terri H.; Feingold, Eleanor; Murray, Jeffrey C.; Marazita, Mary L.; Leslie, Elizabeth J.
Fecha de publicación:
12/2017
Editorial:
Wiley-liss, Div John Wiley & Sons Inc
Revista:
Genetic Epidemiology
ISSN:
0741-0395
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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:
Complex Trait
,
Genetic Modifier
,
Gene-Gene Interaction
,
Orofacial Cleft
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Identificadores
Colecciones
Articulos(CEMIC-CONICET)
Articulos de CENTRO DE EDUCACION MEDICA E INVESTIGACIONES CLINICAS "NORBERTO QUIRNO"
Articulos de CENTRO DE EDUCACION MEDICA E INVESTIGACIONES CLINICAS "NORBERTO QUIRNO"
Citación
Carlson, Jenna C.; Standley, Jennifer; Petrin, Aline; Shaffer, John R.; Butali, Azeez; et al.; Identification of 16q21 as a modifier of nonsyndromic orofacial cleft phenotypes; Wiley-liss, Div John Wiley & Sons Inc; Genetic Epidemiology; 41; 8; 12-2017; 887-897
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