TY - JOUR
T1 - Multivariate GWAS of Structural Dental Anomalies and Dental Caries in a Multi-Ethnic Cohort
AU - Alotaibi, Rasha N.
AU - Howe, Brian J.
AU - Moreno Uribe, Lina M.
AU - Valencia Ramirez, Consuelo
AU - Restrepo, Claudia
AU - Deleyiannis, Frederic W.B.
AU - Padilla, Carmencita
AU - Orioli, Ieda M.
AU - Buxó, Carmen J.
AU - Hecht, Jacqueline T.
AU - Wehby, George L.
AU - Neiswanger, Katherine
AU - Murray, Jeffrey C.
AU - Shaffer, John R.
AU - Weinberg, Seth M.
AU - Marazita, Mary L.
N1 - Publisher Copyright:
Copyright © 2022 Alotaibi, Howe, Moreno Uribe, Valencia Ramirez, Restrepo, Deleyiannis, Padilla, Orioli, Buxó, Hecht, Wehby, Neiswanger, Murray, Shaffer, Weinberg and Marazita.
PY - 2021
Y1 - 2021
N2 - 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 investigative genetic associations for multivariate patterns of correlated dental anomalies and dental caries. Further studies are needed to replicate these results in independent cohorts.
AB - 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 investigative genetic associations for multivariate patterns of correlated dental anomalies and dental caries. Further studies are needed to replicate these results in independent cohorts.
KW - correlation
KW - dental anomalies
KW - dental caries
KW - multi-ethnic
KW - multivariate GWAS
UR - https://www.scopus.com/pages/publications/85150844372
U2 - 10.3389/fdmed.2021.771116
DO - 10.3389/fdmed.2021.771116
M3 - Article
AN - SCOPUS:85150844372
SN - 2673-4915
VL - 2
JO - Frontiers in Dental Medicine
JF - Frontiers in Dental Medicine
M1 - 771116
ER -