Exploratory Genome-Wide Association Study of Dental Arch Shape

Objectives: Malocclusion is the result of vertical, antero-posterior or transverse discrepancies in the relationship of the dental arches. The purpose of this study is to quantify dental arch form and variation at the primary dentition stage, and to use this information to search for novel genes associated with dental arch shape and malocclusion via genome-wide association study (GWAS) data.
Methods: Dental casts from a sample of 305 individuals at the primary dentition stage from the Iowa Fluoride Study were scanned and digitized using 22 gingival margin landmarks to capture shape information and dental arch relationships. 3D coordinate data was submitted to a procrustes fit (in MorphoJ) followed by a relative warps analysis (RWA) to identify key aspects of dental arch shape variation across the sample. A subset of n=237 individuals with GWAS data was analyzed using PLINK to search for phenotype-genotype associations between common genetic variation and the most important aspects of dental arch variation in the sample.
Results: The first 3 relative warps derived from the dental arch landmark dataset address 61.8% of the total shape variation in dental arch form. Linear regression of these shape data with the GWAS data identified many suggestive (p<1.00e-5) hits, with no hits reaching genome-wide significance (p<5.00e-8). The most promising suggestive hits found were rs2707096 (NAV2) with RW1 (vertical and antero-posterior (AP) arch discrepancies), rs10501976 (PGR) with RW2 (AP and medio-lateral (ML) discrepancies), and rs9807432 (DCC) with RW3 (primarily ML and anterior vertical discrepancies).
Conclusions: This study constitutes a preliminary step in the identification of novel genes related to dental arch form and malocclusion. Three of the suggestive SNPs are located close to genes which are expressed in the facial prominences of mice, during development (NAV2, PGR, and DCC). This suggests a potential role for these genes in dental arch form and malocclusion.