Gene–gene interaction between MSX1 and TP63 in Asian case-parent trios with nonsyndromic cleft lip with or without cleft palate

Dongjing Liu, Holger Schwender, Mengying Wang, Hong Wang, Ping Wang, Hongping Zhu, Zhibo Zhou, Jing Li, Tao Wu, Terri L Beaty

Research output: Contribution to journalArticlepeer-review


Background: Small ubiquitin-like modification, also known as sumoylation, is a crucial post-translational regulatory mechanisms involved in development of the lip and palate. Recent studies reported two sumoylation target genes, MSX1 and TP63, to have achieved genome-wide level significance in tests of association with nonsyndromic clefts. Here, we performed a candidate gene analysis considering gene–gene and gene–environment interaction for SUMO1, MSX1, and TP63 to further explore the etiology of nonsyndromic cleft lip with or without cleft palate (NSCL/P). Methods: A total of 130 single-nucleotide polymorphisms (SNPs) in or near SUMO1, MSX1, and TP63 was analyzed among 1,038 Asian NSCL/P trios ascertained through an international consortium. Conditional logistic regression models were used to explore gene–gene (G × G) and gene–environment (G × E) interaction involving maternal environmental tobacco smoke and multivitamin supplementation. Bonferroni correction was used for G × E analysis and permutation tests were used for G × G analysis. Results: While transmission disequilibrium tests and gene–environment interaction analysis showed no significant results, we did find signals of gene–gene interaction between SNPs near MSX1 and TP63. Three pairwise interactions yielded significant p values in permutation tests (rs884690 and rs9290890 with p = 9.34 × 10−5 and empirical p = 1.00 × 10−4, rs1022136 and rs4687098 with p = 2.41 × 10−4 and empirical p = 2.95 × 10−4, rs6819546 and rs9681004 with p = 5.15 × 10−4 and empirical p = 3.02 × 10−4). Conclusion: Gene–gene interaction between MSX1 and TP63 may influence the risk of NSCL/P in Asian populations. Our study provided additional understanding of the genetic etiology of NSCL/P and underlined the importance of considering gene–gene interaction in the etiology of this common craniofacial malformation.

Original languageEnglish (US)
Pages (from-to)317-324
Number of pages8
JournalBirth Defects Research
Issue number4
StatePublished - Mar 1 2018


  • association study
  • case-parent trio
  • gene–gene interaction
  • nonsyndromic cleft lip with or without cleft palate
  • sumoylation

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Embryology
  • Toxicology
  • Developmental Biology
  • Health, Toxicology and Mutagenesis

Fingerprint Dive into the research topics of 'Gene–gene interaction between MSX1 and TP63 in Asian case-parent trios with nonsyndromic cleft lip with or without cleft palate'. Together they form a unique fingerprint.

Cite this