Association analysis of GWAS hits and non-syndromic cleft lip with/without palate with cleft alveolar in Han population of western China.

Cleft alveolar is often accompanied by non-syndromic cleft lip with/without palate (NSCL/P), which could seriously affect the growth and development of the maxilla. In this study, we assessed the associations between 47 susceptible SNPs from previous GWASs of NSCL/P and cleft alveolar in Western Han Chinese population. We recruited 228 trios of NSCL/P with cleft alveolar (156 males and 72 females). The 47 SNPs were genotyped by SNPscan method; Hardy-Weinberg equilibrium test, TDT and parent-of-origin effects were analyzed by PLINK; linkage disequilibrium analysis was conducted by Haploview software. TDT analysis revealed FOXE1 rs894673 (P = 0.0071, ORtransmission = 0.35, 95% CI: 0.16-0.78) and rs3758249 (P = 0.0071, ORtransmission = 0.35, 95% CI: 0.16-0.78) were associated with NSCL/P accompanied cleft alveolar bone. Parent-of-origin effect analysis revealed a paternal special under-transmission of allele A at rs894673 (P = 0.039), allele T at rs3759249 (P = 0.039), and allele T at rs4460498 (P = 0.039) of FOXE1. Allele A at rs987525 showed a significant paternal over-transmission (P = 0.0077). Pairwise LD analysis showed strong LD among rs894673, rs3759249 and rs4460498 (r2 > 0.95, D' = 1). To conclude, our findings indicated that FOXE1 is the susceptible gene for cleft alveolar accompanied by NSCL/P.