Uncovering Molecular and Genetic Drivers of Dental Caries Via scRNA-seq and Mendelian Randomisation

Dental caries remains a prevalent oral health problem globally, influenced by environmental, genetic, and microbial factors. Traditional studies have emphasised microbial colonisation and dietary sugars, neglecting the intricate molecular and genetic interactions. This study aimed to integrate single-cell RNA sequencing (scRNA-seq) with Mendelian randomisation (MR) to elucidate the molecular and genetic factors contributing to the susceptibility and progression of dental caries. We utilised scRNA-seq data from the GSE185222 dataset, comprising both healthy and caries-affected dental pulp tissues, to profile cellular heterogeneity and gene expression. We then applied MR to identify genetic variants linked to caries risk, using Single Nucleotide Polymorphisms (SNPs) as instrumental variables to infer causal relationships between identified genes and caries incidence. Our analyses revealed significant cellular diversity within the dental pulp and identified six key genes (CSF1R, GPX3, LITAF, PLAU, ST8SIA4, and TBXAS1) associated with caries risk. These genes are implicated in immune regulation, oxidative stress response, and tissue remodelling, highlighting a complex interplay between host defense mechanisms and microbial presence. Further, our MR analysis confirmed the causal influence of these genetic variants on caries risk, offering new insights into the genetic predisposition to dental caries. By combining scRNA-seq with MR, this study provides a comprehensive molecular and genetic framework for understanding dental caries. Our findings suggest that targeting these pathways could enhance prevention and treatment strategies, paving the way for precision medicine in dental care. Future research should explore these genes' functional roles in caries progression and their potential as biomarkers for early detection and therapeutic targeting.