Unbiased association and expression studies identify novel genes for tooth development

Previously reported co-occurrence of colorectal cancer (CRC) and tooth agenesis (TA) and the overlap in disease-associated gene variants suggest involvement of similar molecular pathways. In this study, we took an unbiased approach and tested genome-wide significant CRC-associated variants for association with isolated TA. Thirty single nucleotide variants (SNVs) in CRC-predisposing genes/loci were genotyped in a discovery dataset composed of 440 individuals with and without isolated TA. Genome-wide significant associations were found between TA and DUSP10 rs6687758 (P=1.25 x 10-9) and ATF1 rs11169552 (P=4.36 x 10-10), with strong association found with CASC8 rs10505477 (P=8.2 x 10-5). Additional CRC marker haplotypes were also significantly associated with TA (P<0.0002). Genotyping an independent dataset consisting of 52 cases with TA and 427 controls confirmed the association with CASC8.\n\nAtf1 and Dusp10 expression was detected in the mouse developing teeth from early bud stages to the formation of the complete tooth, suggesting a potential role for these genes and their encoded proteins in tooth development. Our findings suggest Atf1 and Dusp10 as new tooth development genes, while having a role in colorectal cancer. While their individual contributions in tooth development remain to be elucidated, these genes may be considered additional candidates to be tested in future human genetic studies.