Exploring the interaction between FGF Genes and T-box genes among chinese nonsyndromic cleft lip with or without cleft palate case-parent trios

Wenyong Li, Mengying Wang, Ren Zhou, Siyue Wang, Hongchen Zheng, Dongjing Liu, Zhibo Zhou, Hongping Zhu, Tao Wu, Terri L Beaty

Research output: Contribution to journalArticle

Abstract

Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a common birth defect. Genetic variants causing syndromic orofacial clefts can also contribute to the etiology of NSCL/P. The purpose of the present study was to explore gene–gene (G × G) interaction using common single nucleotide polymorphic (SNP) markers in fibroblast growth factor (FGF) family and its receptors and T-box genes, which were associated with syndromic orofacial clefts. Our study was conducted in 806 Chinese NSCL/P case-parent trios drawn from an international consortium. A total of 252 SNPs in FGF8, FGF10, FGFR1, FGFR2, and TBX5 passed the quality control criteria and were included in the analysis. The interactions between SNPs in different genes were assessed using Cordell's method, which fitted a conditional logistic regression model. The analysis was performed using the R-package trio (Version 3.8.0). Bonferroni correction was used to adjust for multiple comparisons, and the overall significance threshold was set as P = 1.98 × 10 −4 (0.05/252). Conditional logistic regression revealed the most significant interaction between rs2330542 in FGF10 and rs1946295 in TBX5, which remained significant (P = 9.63 × 10 −6 ) after Bonferroni correction. The relative risk of allele C in rs2330542 (FGF10) was 1.02 (95%CI 0.81–1.28), while the relative risk was 1.42 (95%CI 1.03–1.97) when the exposure was a combination of allele C in rs2330542 and allele A in rs1946295 (TBX5). Our findings confirmed the importance of considering G × G interaction when exploring the genetic risk factors of NSCL/P. Further investigations are warranted to validate the potential interaction and reveal the biological function of FGF10/FGFR2/TBX5. Environ. Mol. Mutagen. 2019.

Original languageEnglish (US)
JournalEnvironmental and Molecular Mutagenesis
DOIs
StatePublished - Jan 1 2019

Fingerprint

Fibroblast Growth Factors
Cleft Lip
Cleft Palate
Logistic Models
Alleles
Single Nucleotide Polymorphism
Genes
Mutagens
Quality Control
Nucleotides

Keywords

  • case-parent trios
  • FGF
  • gene–gene interaction
  • oral clefts
  • T-box genes

ASJC Scopus subject areas

  • Epidemiology
  • Genetics(clinical)
  • Health, Toxicology and Mutagenesis

Cite this

Exploring the interaction between FGF Genes and T-box genes among chinese nonsyndromic cleft lip with or without cleft palate case-parent trios. / Li, Wenyong; Wang, Mengying; Zhou, Ren; Wang, Siyue; Zheng, Hongchen; Liu, Dongjing; Zhou, Zhibo; Zhu, Hongping; Wu, Tao; Beaty, Terri L.

In: Environmental and Molecular Mutagenesis, 01.01.2019.

Research output: Contribution to journalArticle

Li, Wenyong ; Wang, Mengying ; Zhou, Ren ; Wang, Siyue ; Zheng, Hongchen ; Liu, Dongjing ; Zhou, Zhibo ; Zhu, Hongping ; Wu, Tao ; Beaty, Terri L. / Exploring the interaction between FGF Genes and T-box genes among chinese nonsyndromic cleft lip with or without cleft palate case-parent trios. In: Environmental and Molecular Mutagenesis. 2019.
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AU - Wang, Mengying

AU - Zhou, Ren

AU - Wang, Siyue

AU - Zheng, Hongchen

AU - Liu, Dongjing

AU - Zhou, Zhibo

AU - Zhu, Hongping

AU - Wu, Tao

AU - Beaty, Terri L

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AB - Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a common birth defect. Genetic variants causing syndromic orofacial clefts can also contribute to the etiology of NSCL/P. The purpose of the present study was to explore gene–gene (G × G) interaction using common single nucleotide polymorphic (SNP) markers in fibroblast growth factor (FGF) family and its receptors and T-box genes, which were associated with syndromic orofacial clefts. Our study was conducted in 806 Chinese NSCL/P case-parent trios drawn from an international consortium. A total of 252 SNPs in FGF8, FGF10, FGFR1, FGFR2, and TBX5 passed the quality control criteria and were included in the analysis. The interactions between SNPs in different genes were assessed using Cordell's method, which fitted a conditional logistic regression model. The analysis was performed using the R-package trio (Version 3.8.0). Bonferroni correction was used to adjust for multiple comparisons, and the overall significance threshold was set as P = 1.98 × 10 −4 (0.05/252). Conditional logistic regression revealed the most significant interaction between rs2330542 in FGF10 and rs1946295 in TBX5, which remained significant (P = 9.63 × 10 −6 ) after Bonferroni correction. The relative risk of allele C in rs2330542 (FGF10) was 1.02 (95%CI 0.81–1.28), while the relative risk was 1.42 (95%CI 1.03–1.97) when the exposure was a combination of allele C in rs2330542 and allele A in rs1946295 (TBX5). Our findings confirmed the importance of considering G × G interaction when exploring the genetic risk factors of NSCL/P. Further investigations are warranted to validate the potential interaction and reveal the biological function of FGF10/FGFR2/TBX5. Environ. Mol. Mutagen. 2019.

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