Clenching the Strings of Bruxism Etiopathogenesis: Association Analyses on Genetics and Environmental Risk Factors in a Deeply Characterized Italian Cohort

Bruxism is a worldwide oral health problem. Although there is a consensus about its multifactorial nature, its precise etiopathogenetic mechanisms are unclear. This study, taking advantage of a deeply characterized cohort of 769 individuals (aged 6-89 years) coming from Northern Italy's genetically isolated populations, aims to epidemiologically describe environmental risk factors for bruxism development and identify genes potentially involved through a Genome-Wide Association Study (GWAS) approach. Logistic mixed models adjusted for age and sex were performed to evaluate associations between bruxism and possible risk factors, e.g., anxiety, smoking, and alcohol and caffeine intake. A case-control GWAS (135 cases, 523 controls), adjusted for age, sex, and anxiety, was conducted to identify new candidate genes. The GTEx data analysis was performed to evaluate the identified gene expression in human body tissues. Statistical analyses determined anxiety as a bruxism risk factor (OR = 2.54; 95% CI: 1.20-5.38; p-value = 0.015), and GWAS highlighted three novel genes potentially associated with bruxism: NLGN1 (topSNP = rs2046718; p-value = 2.63 × 10-7), RIMBP2 (topSNP = rs571497947; p-value = 4.68 × 10-7), and LHFP (topSNP = rs2324342; p-value = 7.47 × 10-6). The GTEx data analysis showed their expression in brain tissues. Overall, this work provided a deeper understanding of bruxism etiopathogenesis with the long-term perspective of developing personalized therapeutic approaches for improving affected individuals' quality of life.