Target sequencing reveals the association between variants in VAX1 and NSCL/P in Chinese population

Oral Dis. 2023 Jul;29(5):2130-2138. doi: 10.1111/odi.14210. Epub 2022 Apr 21.


Objective: A significant genetic association between rs7078160 in VAX1 and NSCL/P has been established through genome-wide association studies (GWAS), and we previously replicated the association in the Chinese population. The critical issue in the post-GWAS era is to identify functional variations that have a real impact on disease in the susceptible regions highlighted by GWAS. This study aimed to elucidate functional variants in VAX1 fully.

Materials and methods: Firstly, target sequencing was performed on 159 NSCL/P patients, followed by association analysis to discover disease-associated single-nucleotide polymorphisms (SNPs); we then replicated the findings using a larger sample (1626 cases, 2255 controls) and investigated how candidate SNPs affect disease occurrence using extensive annotation databases. Additionally, we compared the genetic profiles of NSCL/P subtypes.

Results: In this study, 6 SNPs in VAX1 were identified to be associated with NSCL/P in the Western Han Chinese population. Five of them were predicted to influence transcriptional factor-biding ability and were expression quantitative trait loci (eQTLs) of nearby genes in multiple tissues.

Conclusion: The previously reported association between rs7078160 and NSCL/P was successfully replicated. Moreover, our findings firstly revealed that 5 SNPs in VAX1 are associated with NSCL/P in the Western Han Chinese population.

Level of evidence: Original Reports.

Keywords: VAX1; association analysis; genetic heterogeneity; non-syndromic cleft lip with or without palate.

MeSH terms

  • Case-Control Studies
  • Cleft Lip* / genetics
  • Cleft Palate* / genetics
  • East Asian People
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genotype
  • Homeodomain Proteins* / genetics
  • Humans
  • Polymorphism, Single Nucleotide
  • Transcription Factors* / genetics


  • Transcription Factors
  • VAX1 protein, human
  • Homeodomain Proteins