Preliminary insights into the association between the well-being spectrum and temporomandibular disorders.

OBJECTIVES: This Mendelian randomization (MR) study aims to explore the causal effect of well-being spectrum on temporomandibular disorders (TMDs). MATERIALS AND METHODS: We employed the largest available summary-level data from genome-wide association studies on the well-being spectrum and its four dimensions-life satisfaction, positive affect, neuroticism and depressive symptoms-along with data on TMDs. Univariable and multivariable MR analyses were used to assess causal effects and their independence from socioeconomic factors, including income, education, and occupation. Additionally, 125 potential mediators were examined for their role in the well-being spectrum-TMDs relationships using two-step MR. RESULTS: A higher well-being spectrum was causally linked to a reduced risk of TMDs, independent of income (OR: 3.39, 95% CI: 1.78-6.43, p < 0.001), education (OR: 3.52, 95% CI: 1.68-7.33, p = 0.001), and occupation (OR: 3.74, 95% CI: 2.12-6.53, p < 0.001). Similar patterns were observed for life satisfaction, positive affect, neuroticism and depressive symptoms. Daily smoking (mediation proportion: 12.9%) and HDL-C (1.8%) were identified as significant mediators. No evidence of pleiotropy was detected (p > 0.05). CONCLUSIONS: A higher well-being spectrum has a protective effect against TMDs, partially mediated by daily smoking and lipid metabolism. CLINICAL RELEVANCE: These findings underscore the critical role of well-being spectrum in the management of TMDs. Among individuals with lower well-being, smokers and those with low HDL-C levels may be at an increased risk for TMDs, warranting focused monitoring and personalized preventive strategies.