Background By age five approximately one-fifth of children have early childhood caries (ECC). Both the oral microbiome and host genetics are thought to influence susceptibility. Whether the oral microbiome modifies genetic susceptibility to ECC has not been tested. We test whether the salivary bacteriome modifies the association of a polygenic score (PGS, a score derived from genomic data that summarizes genetic susceptibility to disease) for primary tooth decay on ECC in the Center for Oral Health Research in Appalachia 2 longitudinal birth cohort.

Methods Children were genotyped using the Illumina Multi-Ethnic Genotyping Array and underwent annual dental examinations. We constructed a PGS for primary tooth decay using weights from an independent, genome-wide association meta-analysis. Using Poisson regression, we tested for associations between the PGS (high vs low) and ECC incidence, adjusting for demographic characteristics (n=783). An incidence-density sampled subset of the cohort (n=138) had salivary bacteriome data at 24-months of age. We tested for effect modification of the PGS on ECC case status by salivary bacterial community state type (CST).

Results By 60-months, 20.69% of children had ECC. High PGS was not associated with an increased rate of ECC (incidence-rate ratio:1.09 (95% confidence interval (CI): 0.83, 1.42)). However, having a cariogenic salivary bacterial CST at 24-months was associated with ECC (odds ratio (OR): 7.48 (95%CI: 3.06, 18.26)), which was robust to PGS adjustment. An interaction existed between the salivary bacterial CST and the PGS on the multiplicative scale (P= 0.04), the PGS was associated with ECC (OR: 4.83 (95% CI: 1.29, 18.17)) only among individuals with a noncariogenic salivary bacterial CST (n=70).

Conclusions Genetic causes of caries phenotypes may be masked by the oral microbiome. As certain salivary bacterial CSTs increased ECC-risk across genetic-risk strata, preventing colonization of cariogenic microbiomes would be universally beneficial.

The authors have declared no competing interest.

This work was funded by the National Institutes for Health, National Institute for Dental and Craniofacial Research grant R01 DE014899. Genotyping of participants was supported by the National Institutes for Health, National Institute for Dental and Craniofacial Research grant X01 HG009878. FB was funded by the National Institutes for Health, National Institute for Dental and Craniofacial Research grant F31 DE029992.

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The 16S rRNA gene amplicon sequencing data from the COHRA2 study is publicly available at the PRJNA752888 repository. Phenotype and host genomic data for the COHRA2 study are available at dbGaP phs001591.v1.p1 upon application.

https://www.ncbi.nlm.nih.gov/bioproject/PRJNA752888