Causal inferences on childhood obesity and dentofacial anomalies: a mendelian randomization study

Background: Dentofacial anomalies, including malocclusion, can lead to functional impairment and psychosocial challenges. While genetics and environmental factors during growth and development play crucial roles, the impact of childhood obesity remains unclear. This study aimed to investigate the causal relationship between high body weight in childhood and dentofacial anomalies using Mendelian randomization (MR). Methods: A two-sample MR approach was applied using genome-wide association study data, which is a technique used in genetic epidemiology to infer causal relationships between exposures and outcomes using summary data from separate genetic association studies for each. This method leverages the random allocation of genes to overcome confounding and reverse causality issues in observational studies, by using genetic variants as instrumental variables. Childhood obesity and body mass index (BMI) were exposures and dentofacial anomalies the outcome. After stringent filtering, 14 childhood obesity and 16 BMI related single nucleotide polymorphisms were selected as instrumental variables for analysis using inverse-variance weighted, MR-Egger, weighted median, weighted mode, and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) methods. To identify potential pleiotropy, the MR-Egger intercept test and the MR-PRESSO global test were applied. Additionally, a leave-one-out sensitivity analysis was conducted to assess the robustness of the findings. Results: Childhood obesity (p = 0.005, Odds Radio (OR) = 0.918 [0.865, 0.974]) and higher BMI (p = 3.72 x 10-6, OR = 0.736 [0.646, 0.838]) were associated with reduced risk of dentofacial anomalies, suggesting a potential causal relationship. Cochrane's Q test, funnel plots, Egger intercept test and MR-PRESSO global test showed no heterogeneity or horizontal pleiotropy. Leave-one-out analysis confirmed result stability. Conclusions: This study provides genetic evidence that childhood obesity and BMI may be associated with a lower incidence of dental/jaw deformities like malocclusion. While an inverse relationship seems to exist, given overall health risks of childhood obesity, this link warrants cautious interpretation and further research.