Gene-Gene Interaction Among WNT Genes for Oral Cleft in Trios

Qing Li, Yoonhee Kim, Bhoom Suktitipat, Jacqueline B. Hetmanski, Mary L. Marazita, Priya Duggal, Terri L Beaty, Joan E. Bailey-Wilson

Research output: Contribution to journalArticle

Abstract

Genome-wide association studies (GWAS) for nonsyndromic cleft lip with or without cleft palate (CL/P) have identified multiple genes as important in the etiology of this common birth defect. We performed a candidate gene/pathway analysis explicitly considering gene-gene (G × G) interaction to further explore the etiology of CL/P. Animal models have shown the WNT signaling pathway plays an important role in mid-facial development, and various genes in this pathway have been associated with nonsyndromic CL/P in previous studies. We propose a combined approach to search for possible G × G interactions using machine learning and regression-based methods to test for interactions between genes in the WNT family, and between these genes and other genes identified by GWAS in case-parent trios. Using this combined approach of regression-based and machine learning methods in CL/P case-parent trios, we found robust evidence of G × G interaction between markers in WNT5B and MAFB (empiric P-values = 0.0076 among Asian trios and P-values = 0.018 among European trios). Additional evidence for epistatic interaction between markers in WNT5A, IRF6, and C1orf107 was seen among Asian trios, and markers in the 8q24 region and WNT5B among European trios.

Original languageEnglish (US)
Pages (from-to)385-394
Number of pages10
JournalGenetic Epidemiology
Volume39
Issue number5
DOIs
StatePublished - Jul 1 2015

Fingerprint

Cleft Palate
Genes
Genome-Wide Association Study
Cleft Lip
Genetic Association Studies
Animal Models
Machine Learning

Keywords

  • Complex disease
  • Family-based study
  • Machine learning

ASJC Scopus subject areas

  • Genetics(clinical)
  • Epidemiology

Cite this

Li, Q., Kim, Y., Suktitipat, B., Hetmanski, J. B., Marazita, M. L., Duggal, P., ... Bailey-Wilson, J. E. (2015). Gene-Gene Interaction Among WNT Genes for Oral Cleft in Trios. Genetic Epidemiology, 39(5), 385-394. https://doi.org/10.1002/gepi.21888

Gene-Gene Interaction Among WNT Genes for Oral Cleft in Trios. / Li, Qing; Kim, Yoonhee; Suktitipat, Bhoom; Hetmanski, Jacqueline B.; Marazita, Mary L.; Duggal, Priya; Beaty, Terri L; Bailey-Wilson, Joan E.

In: Genetic Epidemiology, Vol. 39, No. 5, 01.07.2015, p. 385-394.

Research output: Contribution to journalArticle

Li, Q, Kim, Y, Suktitipat, B, Hetmanski, JB, Marazita, ML, Duggal, P, Beaty, TL & Bailey-Wilson, JE 2015, 'Gene-Gene Interaction Among WNT Genes for Oral Cleft in Trios', Genetic Epidemiology, vol. 39, no. 5, pp. 385-394. https://doi.org/10.1002/gepi.21888
Li Q, Kim Y, Suktitipat B, Hetmanski JB, Marazita ML, Duggal P et al. Gene-Gene Interaction Among WNT Genes for Oral Cleft in Trios. Genetic Epidemiology. 2015 Jul 1;39(5):385-394. https://doi.org/10.1002/gepi.21888
Li, Qing ; Kim, Yoonhee ; Suktitipat, Bhoom ; Hetmanski, Jacqueline B. ; Marazita, Mary L. ; Duggal, Priya ; Beaty, Terri L ; Bailey-Wilson, Joan E. / Gene-Gene Interaction Among WNT Genes for Oral Cleft in Trios. In: Genetic Epidemiology. 2015 ; Vol. 39, No. 5. pp. 385-394.
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