Association of candidate genes with nonsyndromic clefts in Honduran and Colombian populations

Christen J. Lennon, Andrew C. Birkeland, José Arturo Pacheco Nuñez, Gloria H. Su, Patricia Lanzano, Edwin Guzman, Katrina Celis, Sidney B. Eisig, David Hoffman, Maria Teresa Guerra Rendon, Henry Ostos, Wendy K. Chung, Joseph Haddad

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Objectives/Hypothesis: 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. Study Design: 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.

Original languageEnglish (US)
Pages (from-to)2082-2087
Number of pages6
JournalLaryngoscope
Volume122
Issue number9
DOIs
StatePublished - Sep 1 2012
Externally publishedYes

Fingerprint

Single Nucleotide Polymorphism
Cleft Palate
Population
Genes
Genome-Wide Association Study
Hispanic Americans
Cleft Lip
DNA
Case-Control Studies
Alleles

Keywords

  • ABCA4
  • candidate gene
  • Cleft lip
  • cleft palate
  • Colombia
  • FOXE1
  • Honduras
  • MAFB
  • NOG
  • nonsyndromic

ASJC Scopus subject areas

  • Otorhinolaryngology

Cite this

Lennon, C. J., Birkeland, A. C., Nuñez, J. A. P., Su, G. H., Lanzano, P., Guzman, E., ... Haddad, J. (2012). Association of candidate genes with nonsyndromic clefts in Honduran and Colombian populations. Laryngoscope, 122(9), 2082-2087. https://doi.org/10.1002/lary.23394

Association of candidate genes with nonsyndromic clefts in Honduran and Colombian populations. / Lennon, Christen J.; Birkeland, Andrew C.; Nuñez, José Arturo Pacheco; Su, Gloria H.; Lanzano, Patricia; Guzman, Edwin; Celis, Katrina; Eisig, Sidney B.; Hoffman, David; Rendon, Maria Teresa Guerra; Ostos, Henry; Chung, Wendy K.; Haddad, Joseph.

In: Laryngoscope, Vol. 122, No. 9, 01.09.2012, p. 2082-2087.

Research output: Contribution to journalArticle

Lennon, CJ, Birkeland, AC, Nuñez, JAP, Su, GH, Lanzano, P, Guzman, E, Celis, K, Eisig, SB, Hoffman, D, Rendon, MTG, Ostos, H, Chung, WK & Haddad, J 2012, 'Association of candidate genes with nonsyndromic clefts in Honduran and Colombian populations', Laryngoscope, vol. 122, no. 9, pp. 2082-2087. https://doi.org/10.1002/lary.23394
Lennon, Christen J. ; Birkeland, Andrew C. ; Nuñez, José Arturo Pacheco ; Su, Gloria H. ; Lanzano, Patricia ; Guzman, Edwin ; Celis, Katrina ; Eisig, Sidney B. ; Hoffman, David ; Rendon, Maria Teresa Guerra ; Ostos, Henry ; Chung, Wendy K. ; Haddad, Joseph. / Association of candidate genes with nonsyndromic clefts in Honduran and Colombian populations. In: Laryngoscope. 2012 ; Vol. 122, No. 9. pp. 2082-2087.
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abstract = "Objectives/Hypothesis: 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. Study Design: 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.",
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AU - Celis, Katrina

AU - Eisig, Sidney B.

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