# Mendelian Randomization Analysis Reveals No Causal Genetic Link Between Dentofacial Anomalies and Dental Caries

## TL;DR

This study finds no genetic link between dentofacial anomalies and dental caries, suggesting oral hygiene and prevention are key for dental health.

## Contribution

The study uses Mendelian randomization to show no causal genetic relationship between dentofacial anomalies and dental caries.

## Key findings

- No significant causal associations were found between dentofacial anomalies and dental caries.
- Genetic data showed no direct genetic impact of dentofacial anomalies on various dental health issues.
- After removing an outlier, the link between dentofacial anomalies and loose teeth remained non-significant.

## Abstract

Dentofacial anomalies are closely linked to dental health, including caries and periodontal disease. This study examined the potential causal relationship between genetic variations associated with dental anomalies, such as malocclusion, and the risk of dental caries.

A two-sample Mendelian randomization (MR) using genome-wide association studies (GWAS) data was conducted. Dental caries data were obtained from the UKB and GWAS catalog, while dental anomaly data came from FinnGen R12. The primary analysis used inverse-variance weighted (IVW) methods, with weighted median, MR-Egger, and weighted models for validation. Horizontal pleiotropy and outliers were assessed via MR-Egger and MR-PRESSO, while Cochran’s Q test evaluated heterogeneity. Leave-One-Out (LOO) analysis identified predominant instrumental variables (IVs).

The genetic prediction results indicated no statistically significant causal associations between dentofacial anomalies and dental caries (for all three cohorts, p>0.05). Also, IVW indicated no causal associations between dentofacial anomalies and other health problems, including mouth ulcers, toothache, loose teeth, bleeding gums, acute and chronic periodontitis, and painful gums. However, for the outcome of loose teeth, analysis revealed evidence of heterogeneity and suggested potential horizontal pleiotropy, with rs79490532 identified as a outlier. After removing rs79490532, the estimated causal effect of dentofacial anomalies on loose teeth remained statistically non-significant.

Our findings suggest that dentofacial anomalies, including malocclusion, do not have a direct genetic impact on dental health. These results emphasize the importance of prioritizing oral hygiene practices, dietary interventions, and targeted preventive strategies over corrective orthodontic approaches in clinical management to improve dental health outcomes.