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Investigating the genetics of dental caries incidence, development over time, and variability

Zou, Tianyu (2022) Investigating the genetics of dental caries incidence, development over time, and variability. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Dental caries is the most common chronic disease of childhood, worldwide. A better understanding of the etiology of dental caries is needed to improve caries prevention and oral health at both individual and population levels. This study performed GWASs using phenotypes including time-to-first caries incidence and repeated caries measurements at multiple time points, and conducted genome-wide scans of heteroscedasticity in dental caries experience followed by targeted gene-by-environment interaction (GEI) modeling.
Genome-wide survival analysis in Aim 1 showed the genetic underpinnings of caries incidence, with heritability (i.e., the proportion of variance explained by genetics) of time-to-first caries estimated to be 54.4% and 14 association signals identified at the suggestive level (P<1E-5), some of which were located near genes with potential roles in dental caries, including COL5A1, ASIC2, and ESR1. GWAS of repeated dental caries measurements in Aim 2 was the first longitudinal GWAS of caries that demonstrated the genetic influence on caries development over time. The heritability estimate of longitudinal caries trajectories was 54.7%, and there were 1 genome-wide (P<5E-8) and 12 suggestive (P<1E-6) associations, some of which were located near genes with potential functions in caries including SOD2, WNK1, CTSD, WWP2, and BTF3. Genome-wide scans for variance quantitative trait loci (vQTL) – i.e., genetic variants associated with the variance rather than mean of the trait – in Aim 3 identified a total of 39 independent vQTLs, some of which were located in or near genes with potential functions in dental caries (e.g., IGFBP7, SLC5A8, and SHH involved in tooth development and enamel mineralization). In the GEI analysis using the prioritized vQTLs and self-reported environmental factors, we found that children with certain genotypes of prioritized variants exhibited higher caries experience if they had lower parental educational attainment, had lower household/parental income, brushed their teeth less frequently, consumed sugar-sweetened beverages more frequently, were not breastfed, and were female.
This study has broadened our knowledge of the genetic architecture of caries onset and development over time, as well as GEI, and may provide the foundation for better early detection, risk assessment, dental care, and effective public health interventions.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Zou, Tianyutiz45@pitt.edutiz450000-0002-2249-5871
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairShaffer, John R.john.r.shaffer@pitt.edujohn.r.shaffer
Committee MemberMinster, Ryan L.rminster@pitt.edurminster
Committee MemberWeinberg, Seth M.smwst46@pitt.edusmwst46
Committee MemberMarazita, Mary L.marazita@pitt.edumarazita
Date: 1 July 2022
Date Type: Publication
Defense Date: 27 May 2022
Approval Date: 1 July 2022
Submission Date: 15 June 2022
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 182
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Human Genetics
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Dental caries, genetics, genome-wide association, risk factors
Date Deposited: 01 Jul 2022 18:39
Last Modified: 01 Jul 2022 18:39


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