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Investigating the Genetics of Dental Caries Incidence, Development Over Time, and Variability.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Investigating the Genetics of Dental Caries Incidence, Development Over Time, and Variability./
作者:	Zou, Tianyu.
面頁冊數:	1 online resource (183 pages)
附註:	Source: Dissertations Abstracts International, Volume: 84-04, Section: B.
Contained By:	Dissertations Abstracts International84-04B.
標題:	Socioeconomic factors. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=29402222click for full text (PQDT)
ISBN:	9798352647011

Investigating the Genetics of Dental Caries Incidence, Development Over Time, and Variability.
Zou, Tianyu.

Investigating the Genetics of Dental Caries Incidence, Development Over Time, and Variability. - 1 online resource (183 pages)

Source: Dissertations Abstracts International, Volume: 84-04, Section: B.

Thesis (Ph.D.)--University of Pittsburgh, 2022.

Includes bibliographical references

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<1E5), 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.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2023

Mode of access: World Wide Web

ISBN: 9798352647011Subjects--Topical Terms:

3435444
Socioeconomic factors.
Index Terms--Genre/Form:

542853
Electronic books.

Investigating the Genetics of Dental Caries Incidence, Development Over Time, and Variability.
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520 $a 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<1E5), 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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