Alotaibi, Rasha
(2019)
GENETIC ANALYSES OF DENTAL ANOMALIES AND DENTAL CARIES IN MULTIETHNIC POPULATIONS.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Tooth development is a long and complex process of several stages that starts between the sixth and eighth weeks in utero. Disruption during any of these stages can result in dental anomalies and/or increased risk of oral diseases such as dental caries. Previous studies indicate that genetic factors play an important role in the etiology of dental anomalies of size, shape, number, position, and of oral diseases including dental caries. Furthermore, previous studies have also shown that some dental anomalies are associated with each other in the same patient, suggesting that they may share common etiologic components.
This study evaluated the relationships between several structural dental anomalies and dental caries across the multi-ethnic cohort from The Pittsburgh Orofacial Cleft study (POFC; N= 3579), performed genome-wide association scans (GWAS) in POFC, including the multivariate approach of GWAS for the associated dental anomalies and dental caries, and performed GWAS for each of the included dental anomalies in POFC. Finally, we performed GWAS of dental caries in two cohorts; (POFC; N= 3579), and a cohort from The Center for Oral Health Research in Appalachia (COHRA1, N=1763), along with subsequent meta-analysis.
We found intercorrelations between four subsets of dental phenotypes: Agenesis, Impaction and Rotation (AIR); Hypoplasia, Displacement and Rotation (HDR); Displacement, Rotation and Mammalons (DRM); and Dental caries, Agenesis and Hypoplasia (DAH). This was the first study to investigative genetic associations for multivariate patterns of correlated dental anomalies and dental caries, and we were able to identify suggestive association signals (P < 1 X 10E-05) near genes with biological roles during tooth development; ADAMTS9 and PRICKLE2 were associated with AIR; GLIS3, WDR72, and ROR2 were associated with HDR and DRM; ROBO2 was associated with DRM, BMP7 was associated with HDR; and ROBO1, SMAD2 and MSX2 were associated with DAH. We were also able to identify risk loci associated with each of the structural dental anomalies separately.
This is one of the largest multi-ethnic GWAS study of dental caries that helped in discovering several novel loci containing genes with plausible biological roles in tooth development and/or oral dental caries; such as REL gene (P = 3.91E-09) and were also able to confirm some of the previously identified genes (MPPED2, P = 2.36E−6; NEED9, P = 7.60E-06) that has been associated with dental caries.
Further studies are needed to replicate the results of this study in an independent cohort, which is strongly recommended. In addition, studies are needed to investigate the biological roles of these nominated genes, in human and animal models to fully understand their relevance to tooth development process and dental caries.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
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| ETD Committee: |
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| Date: |
6 December 2019 |
| Date Type: |
Publication |
| Defense Date: |
31 October 2019 |
| Approval Date: |
6 December 2019 |
| Submission Date: |
11 November 2019 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
215 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Dental Medicine > Dental Science |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Dental anomalies, Multivariate, GWAS, Dental Caries |
| Date Deposited: |
06 Dec 2019 14:43 |
| Last Modified: |
06 Dec 2019 14:43 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/37771 |
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