Association Study of Wnt Pathway Genes with Non-syndromic Orofacial Cleft in Han Chinese

ObjectiveTo investigate the association between Wnt signaling pathway genes and non-syndromic orofacial cleft (NSOC) in the Han Chinese population.DesignBased on a previously published genome-wide association study (GWAS), we performed a discovery phase analysis on 635 QC-passed SNPs (out of 7054 initially extracted from 59 Wnt pathway genes). Significant loci were then validated in an independent replication cohort.SettingA specialized craniofacial surgery center within a tertiary care institution.Patients/ParticipantsIn the discovery phase, we extracted the genotype data of 2512 NSOC cases and 2255 controls from two previous published GWASs. The independent replication cohort included 2724 patients with NSOC and 1263 healthy controls, all of Han Chinese descent.InterventionsNo clinical interventions were applied; the study involved genetic data analysis only.Main Outcome MeasuresSNPs associated with NSOC and its subtypes were identified through allelic and genotypic association analyses, with odds ratios (ORs), 95% confidence intervals (CIs), and P-values calculated.ResultsIn the independent replication cohort, rs4821611 in RAC2 was significantly associated with NSOC (P = 5.8 × 10^-7, OR = 0.77, 95% CI: 0.70-0.85), NSCL/P (P = 4.4 × 10^-11, OR = 0.68, 95%CI: 0.61-0.77), and NSCLO (P = 3.27 × 10^-15, OR = 0.6, 95% CI: 0.53-0.68). Genotypic analysis confirmed these associations. rs757190 in WNT3 was also associated with NSCLP (P = 0.00056, OR = 0.78, 95% CI: 0.67-0.90).Conclusionsrs4821611 in RAC2 and rs757190 in WNT3 are associated with NSOC and its subtypes in the Han Chinese population, supporting a role for Wnt signaling in cleft pathogenesis.