Testing candidate genes for non-syndromic oral clefts using a case-parent trio design

T. H. Beaty, J. B. Hetmanski, J. S. Zeiger, Y. T. Fan, K. Y. Liang, C. A. VanderKolk, I. McIntosh

Research output: Contribution to journalArticlepeer-review

82 Scopus citations


Markers in five candidate genes were examined on 269 case-parent trios ascertained through a child with an isolated, non-syndromic oral cleft (cleft lip, CL; cleft palate, CP; or cleft lip and palate, CLP). Cases and their parents were ascertained through treatment centers in Maryland. Markers at two of the five candidate genes, transforming growth factor β3 (TGFβ3) and MSX1, showed consistent evidence of linkage and disequilibrium due to linkage using several statistical tests (e.g., the global chi-square for TGFβ3 was 21.1 with 12 df, P = 0.03; that for MSX1 was 8.7 with 3 df, P = 0.03). There was little evidence of heterogeneity in the role of TGFβ3 between different types of oral clefts, but MSX1 did yield marginal evidence for such heterogeneity. MSX1 also showed evidence for interaction between infant's genotype and maternal smoking, giving a likelihood ratio test for heterogeneity between smoker and non-smoker mothers of 7.16 (2 df, P = 0.03). Using a conditional logistic model to test for gene-gene interaction showed no evidence of interaction between TGFβ3 and MSX1, with both seeming to contribute independently to risk of isolated, non-syndromic oral clefts.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalGenetic epidemiology
Issue number1
StatePublished - Jan 10 2002


  • Case-parent trio design
  • MSX1
  • Maternal smoking
  • Oral clefts
  • Transforming growth factor β3

ASJC Scopus subject areas

  • Epidemiology
  • Genetics(clinical)


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