LAUSR

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.