Alotaibi Rasha N, Howe Brian J, Moreno Uribe Lina M, Ramirez Consuelo Valencia, Restrepo Claudia, Deleyiannis Frederic W B, Padilla Carmencita, Orioli Ieda M, Buxó Carmen J, Hecht Jacqueline T, Wehby George L, Neiswanger Katherine, Murray Jeffery C, Shaffer John R, Weinberg Seth M, Marazita Mary L
Dental Health Department, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia.
Center for Craniofacial and Dental Genetics, Department of Oral and Craniofacial Sciences, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Front Dent Med. 2021;2. doi: 10.3389/fdmed.2021.771116. Epub 2022 Jan 4.
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 ( = 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 ( = 2,187) and unaffected controls ( = 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 ( < 10) near genes with known biological roles during tooth development, including and associated with AIR; , , and associated with HDR and DRM; associated with DRM; associated with HDR; and , and 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.
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