Non-syndromic cleft lip with or without palate susceptible loci is associated with tooth agenesis

Objective Non-syndromic tooth agenesis (NSTA) may share common genetic factors with non-syndromic cleft lip with or without cleft palate (NSCL/P). Single-nucleotide polymorphisms (SNPs) were associated with individual's susceptibility to these anomalies. We selected five NSCL/P-associated SNPs from our previous genome-wide association study (GWAS) to test for the associations with NSTA. Materials and methods A total of 677 NSTA cases and 1,144 healthy controls were recruited in this case-control study. Five genome-wide NSCL/P-associated SNPs (rs2235371, rs7078160, rs8049367, rs4791774, and rs13041247) were genotyped by TaqMan platform and evaluated for the associations with NSTA using plink software. Results No significant associations between these SNPs and risk of NSTA were observed in the overall analysis and subgroup analysis with the number of missing teeth. However, in the subgroup analysis by tooth position, rs8049367 was nominally associated with mandibular premolar agenesis (Dominant model: ORdom = 0.66, 95% CIdom = 0.47-0.93, p(dom) = 0.016; Heterozygote model: ORhet = 0.60, 95% CIhet = 0.41-0.88, P-het = 0.008). Rs4791774 showed a nominal association with congenitally missing maxillary canine (Dominant model: ORdom = 0.53, 95% CIdom = 0.28-0.98, p(dom) = 0.041; Heterozygote model: ORhet = 0.50, 95% CIhet = 0.26-0.97, P-het = 0.041) and premolar (Additive model: OR = 0.59, 95% CI = 0.36-0.96, p = 0.035). Conclusion This study showed that NSCL/P susceptible loci rs8049367 and rs4791774 were probably associated with the risk of NSTA.