GWAS reveals new recessive loci associated with non- syndromic facial clefting

ABSTRACT: We have applied a GWAS to 40 consanguineous families segregating cases of non-syndromic cleft lip with or without cleft palate (NS CL/P) (a total of 160 affected and unaffected individuals) in order to trace potential recessive loci that confer susceptibility to this common facial malformation. Pedigree-based association test (PBAT) analyses reported nominal evidence of association and linkage over SNP markers located at 11q25 (rs4937877, P = 2.7 × 10−6), 19p12 (rs4324267, P = 1.6 × 10−5), 5q14.1 (rs4588572, P-value = 3.36 × 10−5), and 15q21.1 (rs4774497, P = 1.08 × 10−4). Using the Versatile Gene-Based Association Study to complement the PBAT results, we found clusters of markers located at chromosomes 19p12, 11q25, and 8p23.2 overcome the threshold for GWAS significance (P < 1 × 10−7). From this study, new recessive loci implicated in NS CL/P include: B3GAT1, GLB1L2, ZNF431, ZNF714, and CSMD1, even though the functional association with the genesis of NS CL/P remains to be elucidated. These results emphasize the importance of using homogeneous populations, phenotypes, and family structures for GWAS combined with gene-based association analyses, and should encourage. other researchers to evaluate these genes on independent patient samples affected by NS CL/P.

• Autores: Camargo Guerrero, Mauricio; Rivera Valencia, Dora; Moreno Uribe, Lina María; Lidral, Andrew; Harperd, Ursula; Jones, Marypat; Solomone, Benjamin D.; Roessler, Erich; Vélez Valbuena, Jorge Iván; Martínez, Ariel F.; Chandrasekharappa, Settara C.; Arcos Burgos, Oscar Mauricio
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2012
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/42330
• Acceso en línea: https://hdl.handle.net/10495/42330
• Palabra clave: Encéfalo - anomalías; Brain - abnormalities; Estudios de Casos y Controles; Case-Control Studies; Labio Leporino; Cleft Lip; Fisura del Paladar; Cleft Palate; Proteínas de Unión al ADN; DNA-Binding Proteins; Genes Recesivos; Genes, Recessive; Predisposición Genética a la Enfermedad; Genetic Predisposition to Disease; Estudio de Asociación del Genoma Completo; Genome-Wide Association Study; Glucuronosiltransferasa; Glucuronosyltransferase; Glicósido Hidrolasas; Glycoside Hydrolases; Factores de Transcripción; Transcription Factors; Proteínas Supresoras de Tumor; Tumor Suppressor Proteins; https://id.nlm.nih.gov/mesh/D001921; https://id.nlm.nih.gov/mesh/D016022; https://id.nlm.nih.gov/mesh/D002971; https://id.nlm.nih.gov/mesh/D002972; https://id.nlm.nih.gov/mesh/D004268; https://id.nlm.nih.gov/mesh/D005808; https://id.nlm.nih.gov/mesh/D020022; https://id.nlm.nih.gov/mesh/D055106; https://id.nlm.nih.gov/mesh/D014453; https://id.nlm.nih.gov/mesh/D006026; https://id.nlm.nih.gov/mesh/D014157; https://id.nlm.nih.gov/mesh/D025521
• Rights: openAccess
• License: http://creativecommons.org/licenses/by-nc-nd/2.5/co/