A Genome-wide association study of premolar agenesis in a chinese population.

OBJECTIVE: Premolar agenesis is a common subtype of tooth agenesis. Although a genome-wide study (GWAS) has identified some variants involved in tooth agenesis in Europeans, the genetic mutation related to premolar agenesis in the Chinese population remains unclear. MATERIALS AND METHODS: We present a GWAS in 218 premolar agenesis cases and 1,222 controls using the Illumina Infinium® Global Screening Array. 5,585,618 single nucleotide polymorphisms (SNPs) were used for tests of associations with premolar agenesis. RESULTS: Four independent SNPs on chromosome 2 were identified as susceptibility loci, including rs147680216, rs79743039, rs60540881, and rs6738629. The genome-wide significant SNP rs147680216 (p = 6.09 × 10-9 ) was predicted to change the structure of the WNT10A protein and interact with hedgehog signaling pathway components. Meta-analysis showed that the rs147680216 A allele significantly increased the risk of tooth agenesis (p = 0.000). The other three SNPs with nominal significance are novel susceptibility loci. Of them, rs6738629 (p = 5.40 × 10-6 ) acts as a potential transcriptional regulator of GCC2, a gene playing a putative role in dental and craniofacial development. CONCLUSION: Our GWAS indicates that rs147680216 and additional three novel susceptibility loci on chromosome 2 are associated with the risk of premolar agenesis in the Chinese population.