Abstract
Odontogenesis is a complex process, where disruption can result in dental anomalies and/or increase the risk of developing dental caries. Based on previous studies, certain dental anomalies tend to co-occur in patients, suggesting that these traits may share common genetic and etiological components. The main goal of this study was to implement a multivariate genome-wide association study approach to identify genetic variants shared between correlated structural dental anomalies and dental caries. Our cohort (N = 3,579) was derived from the Pittsburgh Orofacial Clefts Study, where multiple dental traits were assessed in both the unaffected relatives of orofacial cleft (OFC) cases (n = 2,187) and unaffected controls (n = 1,392). We identified four multivariate patterns of correlated traits in this data: tooth agenesis, impaction, and rotation (AIR); enamel hypoplasia, displacement, and rotation (HDR); displacement, rotation, and mamelon (DRM); and dental caries, tooth agenesis and enamel hypoplasia (CAH). We analyzed each of these four models using genome-wide multivariate tests of association. No genome-wide statistically significant results were found, but we identified multiple suggestive association signals (P < 10-5) near genes with known biological roles during tooth development, including ADAMTS9 and PRICKLE2 associated with AIR; GLIS3, WDR72, and ROR2 associated with HDR and DRM; ROBO2 associated with DRM; BMP7 associated with HDR; and ROBO1, SMAD2, and MSX2 associated with CAH. This is the first study to investigate genetic associations for multivariate patterns of correlated dental anomalies and dental caries. Further studies are needed to replicate these results in independent cohorts.
Highlights
Odontogenesis, the process of tooth development, is a complicated process that starts early in embryogenesis [1, 2]
Our study showed that there was a trend for higher rates of dental caries among unaffected relatives vs. controls (DFT/dft percentage = 62.58 vs. 37.42%, P = 0.0018)
We observed a trend for an increased rate in unaffected relatives for impaction (80.49 vs. 19.51%, P = 0.01), supernumerary teeth (84.62 vs. 15.38%, P = 0.014), and dental caries (78.40 vs. 62.58%, P = 0.0018) compared with controls
Summary
Odontogenesis, the process of tooth development, is a complicated process that starts early in embryogenesis [1, 2]. Disturbances during the signaling process or changes in any of the regulating genes may result in dental anomalies, including changes in tooth development, structure, number, size, and morphology [5, 6]. Structural dental anomalies, such as tooth agenesis, enamel hypoplasia, impaction, rotation, displacement, mamelons, and supernumerary teeth (Supplementary Table 1 provides definitions for the dental anomalies used in this study) are presumed to be caused by interactions between genetic, epigenetic, and environmental factors during the process of tooth development [7]. Some dental anomalies might be asymptomatic, these anomalies can lead to serious clinical problems, including delayed eruption or impaction of the teeth; temporomandibular joint pain and dysfunction; malocclusion; periodontal disease due to excessive occlusal force; and increased susceptibility to dental caries due to defects in tooth structure and/or crowding [10]
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