title: Association of candidate genes with nonsyndromic clefts in Honduran and Colombian populations.
abstract: OBJECTIVE
  Orofacial clefts are the most common craniofacial birth defects in humans, with the majority of orofacial clefts occurring as nonsyndromic cleft lip with or without cleft palate (NSCLP). We previously demonstrated associations between single-nucleotide polymorphisms (SNPs) in the IRF6 gene and NSCLP in the Honduran population. Here we investigated other candidate genes and chromosomal regions associated with NSCLP identified from genome-wide association studies (GWAS), including MAFB, ABCA4, 8q24, 9q22, 10q25, and 17q22 in two independent Hispanic populations.
  
  
  METHODS
  Case-control and family-based association testing.
  
  
  METHODS
  Honduran families with two or more members with NSCLP (multiplex) were identified. DNA was collected from affected and unaffected family members (488) and 99 gender-matched controls. NSCLP Colombian families were identified; DNA was collected from 26 proband-parent trios. All participants were genotyped for 17 SNPs in six chromosomal regions. Case-control association and family-based association testing (FBAT) analyses were conducted.
  
  
  RESULTS
  Seven SNPs demonstrated association in at least one model in the Honduran population. In the Colombian families, five SNPs demonstrated significance in FBAT when patients with isolated cleft palate (CP) were included; four overlapped with SNPs demonstrating significance in the Honduran population, two with the same allele. One SNP retained significance with CP excluded.
  
  
  CONCLUSIONS
  This study supports the previous GWAS findings and is the first to suggest a role for FOXE1, ABCA4, and MAFB in orofacial clefting in two separate Hispanic populations.
authors: Columbia University College of Physicians and Surgeons, New York, New York, USA.
authors: Christen J
authors: CJ
authors: Lennon
authors: Andrew C
authors: AC
authors: Birkeland
authors: José Arturo Pacheco
authors: JA
authors: Nuñez
authors: Gloria H
authors: GH
authors: Su
authors: Patricia
authors: P
authors: Lanzano
authors: Edwin
authors: E
authors: Guzman
authors: Katrina
authors: K
authors: Celis
authors: Sidney B
authors: SB
authors: Eisig
authors: David
authors: D
authors: Hoffman
authors: Maria Teresa Guerra
authors: MT
authors: Rendon
authors: Henry
authors: H
authors: Ostos
authors: Wendy K
authors: WK
authors: Chung
authors: Joseph
authors: J
authors: Haddad
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000483:Alleles; D016022:Case-Control Studies; D002971:Cleft Lip / Q000208:ethnology / Q000235:genetics* / Q000601:surgery; D002972:Cleft Palate / Q000208:ethnology / Q000235:genetics* / Q000601:surgery; D003105:Colombia / Q000208:ethnology; D016001:Confidence Intervals; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D055106:Genome-Wide Association Study; D005838:Genotype; D006630:Hispanic or Latino / Q000235:genetics; D006721:Honduras / Q000208:ethnology; D006801:Humans; D015994:Incidence; D050835:Interferon Regulatory Factors / Q000235:genetics; D051258:MafB Transcription Factor / Q000235:genetics*; D008297:Male; D016017:Odds Ratio; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D014481:United States / Q000453:epidemiology
chemical_list: C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters; C106894:FOXE1 protein, human; D051858:Forkhead Transcription Factors; D050835:Interferon Regulatory Factors; C490407:MAFB protein, human; D051258:MafB Transcription Factor