Potential risk factors and genetic variants associated with dental caries incidence in Appalachia using genome-wide survival analysis

Tianyu Zou; Katherine Neiswanger; Eleanor Feingold; Betsy Foxman; Daniel W McNeil; Mary L Marazita; John R Shaffer

Potential risk factors and genetic variants associated with dental caries incidence in Appalachia using genome-wide survival analysis

Int J Mol Epidemiol Genet. 2023 Aug 15;14(2):19-33. eCollection 2023.

Authors

Tianyu Zou¹, Katherine Neiswanger², Eleanor Feingold^{1

3}, Betsy Foxman⁴, Daniel W McNeil⁵, Mary L Marazita^{1

2

6}, John R Shaffer^{1

2}

Affiliations

¹ Department of Human Genetics, School of Public Health, University of Pittsburgh Pittsburgh, PA, USA.
² Center for Craniofacial and Dental Genetics, Department of Oral and Craniofacial Sciences, School of Dental Medicine, University of Pittsburgh Pittsburgh, PA, USA.
³ Department of Biostatistics, School of Public Health, University of Pittsburgh Pittsburgh, PA, USA.
⁴ Center for Molecular and Clinical Epidemiology of Infectious Diseases, Department of Epidemiology, University of Michigan School of Public Health Ann Arbor, MI, USA.
⁵ Department of Community Dentistry and Behavioral Science, College of Dentistry, University of Florida Gainesville, FL, USA.
⁶ Clinical and Translational Sciences, School of Medicine, University of Pittsburgh Pittsburgh, PA, USA.

PMID: 37736056
PMCID: PMC10509536

Abstract

Objective: The aim of this study was to identify the potential risk factors and genetic variants associated with dental caries incidence using survival analysis.

Methods: The Center for Oral Health Research in Appalachia recruited and prospectively followed pregnant women and their children. A total of 909 children followed from birth for up to 7 years were included in this study. Annual intra-oral examinations were performed to assess dental caries experience including the approximate time to first caries incidence in the primary dentition. Cox proportional hazards models were used to assess the associations of time to first caries incidence with self-reported risk factors and 4.9 million genetic variants ascertained using a genome-wide genotyping array.

Results: A total of 196 of 909 children (21.56%) had their first primary tooth caries event during follow-up. Household income, home water source, and mother's educational attainment were significantly associated with time to first caries incidence in the stepwise Cox model. The heritability (i.e., proportion of variance explained by genetics) of time to first caries was 0.54. Though no specific genetic variants were associated at the genome-wide significance level (P < 5E-8), we identified 14 loci at the suggestive significance level (5E-8 < P < 1E-5), some of which were located within or near genes with plausible biological functions in dental caries.

Conclusion: Our findings indicate that household income, home water source, and mother's educational attainment are independent risk factors for dental caries incidence. We nominate several suggestive loci for further investigation.

Keywords: Risk factors; bioinformatics; child dentistry; epidemiology; genetics; genomics.