Events Calendar

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

Department of Human Genetics Doctoral Candidate, Tianyu Zou, defends her dissertation on “Investigating the Genetics of Dental Caries Incidence, Development Over Time, and Variability” 

ADVISOR: John R. Shaffer, PhD

Committee Members:

  • Ryan L. Minster, PhD, MSIS
  • Seth M. Weinberg, PhD
  • Mary L. Marazita, PhD

 

ABSTRACT:

Dental caries is the most common chronic disease of childhood, worldwide, and is a complex disease influenced by multiple factors including environmental, behavioral, and genetic factors. A better understanding of the etiology of dental caries is needed to improve caries prevention and oral health at both individual and population levels.

Genome-wide association studies (GWASs) have been used to explore the genetic basis of dental caries in the past decade and have reported several genes with plausible biological roles in dental caries. However, prior GWASs of dental caries used phenotypes collected at a single time point, which neglected the aspects of caries incidence and development over time. Additionally, GWASs of quantitative phenotypes only tested the genetic effects on the phenotypic mean, not the phenotypic variability. To fill these gaps, this study performed GWASs using phenotypes including time-to-first caries incidence and repeated caries measurements at multiple time points, which were generated from cohorts with longitudinal caries assessments, and conducted genome-wide scans of heteroscedasticity in dental caries experience followed by targeted gene-by-environment interaction (GEI) modeling.

Specifically, 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 54.5% and 14 association signals identified at the suggestive level (P<1E-5), some of which were located near genes with potential roles in caries, including COL5A1, ASIC2, 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, 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 variants with genetic effects on caries variability, which were prioritized for detecting GEI in dental caries.

The public health significance of this research is that the results of this study have 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.

Dial-In Information

ZOOM Virtual/Online Event – All Welcome (Advance Registration Required) https://pitt.co1.qualtrics.com/jfe/form/SV_0oiEXm3wu1wTVn8

Friday, May 27 at 10:00 a.m. to 12:00 p.m.

Virtual Event

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

Department of Human Genetics Doctoral Candidate, Tianyu Zou, defends her dissertation on “Investigating the Genetics of Dental Caries Incidence, Development Over Time, and Variability” 

ADVISOR: John R. Shaffer, PhD

Committee Members:

  • Ryan L. Minster, PhD, MSIS
  • Seth M. Weinberg, PhD
  • Mary L. Marazita, PhD

 

ABSTRACT:

Dental caries is the most common chronic disease of childhood, worldwide, and is a complex disease influenced by multiple factors including environmental, behavioral, and genetic factors. A better understanding of the etiology of dental caries is needed to improve caries prevention and oral health at both individual and population levels.

Genome-wide association studies (GWASs) have been used to explore the genetic basis of dental caries in the past decade and have reported several genes with plausible biological roles in dental caries. However, prior GWASs of dental caries used phenotypes collected at a single time point, which neglected the aspects of caries incidence and development over time. Additionally, GWASs of quantitative phenotypes only tested the genetic effects on the phenotypic mean, not the phenotypic variability. To fill these gaps, this study performed GWASs using phenotypes including time-to-first caries incidence and repeated caries measurements at multiple time points, which were generated from cohorts with longitudinal caries assessments, and conducted genome-wide scans of heteroscedasticity in dental caries experience followed by targeted gene-by-environment interaction (GEI) modeling.

Specifically, 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 54.5% and 14 association signals identified at the suggestive level (P<1E-5), some of which were located near genes with potential roles in caries, including COL5A1, ASIC2, 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, 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 variants with genetic effects on caries variability, which were prioritized for detecting GEI in dental caries.

The public health significance of this research is that the results of this study have 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.

Dial-In Information

ZOOM Virtual/Online Event – All Welcome (Advance Registration Required) https://pitt.co1.qualtrics.com/jfe/form/SV_0oiEXm3wu1wTVn8

Friday, May 27 at 10:00 a.m. to 12:00 p.m.

Virtual Event

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