title: 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.
authors: Population Genetics and Mutacarcinogenesis Group, University of Antioquia, Medellin, Colombia.
authors: Mauricio
authors: M
authors: Camargo
authors: Dora
authors: D
authors: Rivera
authors: Lina
authors: L
authors: Moreno
authors: Andrew C
authors: AC
authors: Lidral
authors: Ursula
authors: U
authors: Harper
authors: Marypat
authors: M
authors: Jones
authors: Benjamin D
authors: BD
authors: Solomon
authors: Erich
authors: E
authors: Roessler
authors: Jorge I
authors: JI
authors: Vélez
authors: Ariel F
authors: AF
authors: Martinez
authors: Settara C
authors: SC
authors: Chandrasekharappa
authors: Mauricio
authors: M
authors: Arcos-Burgos
mesh_terms: D001921:Brain / Q000002:abnormalities; D016022:Case-Control Studies; D002971:Cleft Lip / Q000453:epidemiology / Q000235:genetics*; D002972:Cleft Palate / Q000453:epidemiology / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005808:Genes, Recessive; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study; D014453:Glucuronosyltransferase / Q000235:genetics; D006026:Glycoside Hydrolases / Q000235:genetics; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D010375:Pedigree; D014157:Transcription Factors / Q000235:genetics; D025521:Tumor Suppressor Proteins
chemical_list: C477880:CSMD1 protein, human; D004268:DNA-Binding Proteins; D005819:Genetic Markers; D008565:Membrane Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C581788:ZNF431 protein, human; C581787:ZNF714 protein, human; C111364:galactosylgalactoylxylosylprotein 3-beta-glucuronosyltransferase; D014453:Glucuronosyltransferase; D006026:Glycoside Hydrolases; C581786:GLB1L2 protein, human