Sleep bruxism (SB) affects a considerable part of the population and is associated with neuroticism, stress, and anxiety in various studies. However, the causal mechanisms between neuroticism and SB have not been examined. Understanding the reasons for SB is important as understanding bruxism may allow improved comprehensive management of the disorders and comorbidities related to it. Previous studies on the association of risk factors to SB have provided important symptomatic insight but were mainly questionnaire based or limited in sample size and could not adequately assess causal relationships. The aim of this study was to elaborate the possible causal relationship of neuroticism as a risk factor for SB through a Mendelian randomization (MR) approach by combining questionnaires, registry data, and genetic information in large scale. We performed a two-sample MR study using instrumental genetic variants of neuroticism, including neuroticism subcategories, in the UK Biobank ( n = 380,506) and outcome data of probable SB using FinnGen ( n [cases/controls] = 12,297/364,980). We discovered a causal effect from neuroticism to SB (odds ratio [OR] = 1.38 [1.10–1.74], P = 0.0057). A phenotype sensitive to stress and adversity had the strongest effect (OR = 1.59 [1.17–2.15], P = 0.0028). Sensitivity analyses across MR methods supported a causal relationship, and we did not observe pleiotropy between neuroticism and SB (MR-Egger intercept, P = 0.87). Our findings are in line with earlier observational studies that connect stress and SB. Furthermore, our results provide evidence that neurotic traits increase the risk of probable SB.

中文翻译：

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神经质和睡眠磨牙症的双样本孟德尔随机研究


睡眠磨牙症 (SB) 影响着相当一部分人群，多项研究表明它与神经质、压力和焦虑有关。然而，神经质与 SB 之间的因果机制尚未得到研究。了解 SB 的原因很重要，因为了解磨牙症可能有助于改善与其相关的疾病和合并症的综合管理。先前关于危险因素与 SB 关联的研究提供了重要的症状见解，但主要是基于问卷调查或样本量有限，无法充分评估因果关系。本研究的目的是通过孟德尔随机化（MR）方法，结合大规模问卷、登记数据和遗传信息，详细阐述神经质作为 SB 危险因素的可能因果关系。我们使用英国生物银行 (n = 380,506) 中神经质的工具遗传变异（包括神经质子类别）和 FinnGen 的可能 SB 的结果数据（n [病例/对照] = 12,297/364,980）进行了两个样本的 MR 研究。我们发现神经质与 SB 存在因果关系（比值比 [OR] = 1.38 [1.10–1.74]，P = 0.0057）。对压力和逆境敏感的表型具有最强的影响（OR = 1.59 [1.17–2.15]，P = 0.0028）。 MR 方法的敏感性分析支持因果关系，并且我们没有观察到神经质和 SB 之间的多效性（MR-Egger 截距，P = 0.87）。我们的研究结果与早期将压力和情绪联系起来的观察性研究一致。此外，我们的结果提供了证据表明神经质特征会增加可能发生 SB 的风险。