Associations between temporomandibular disorders/bruxism and head and neck pains: a bidirectional Mendelian randomization study

J Oral Facial Pain Headache. 2025 Dec;39(4):122-137. doi: 10.22514/jofph.2025.070. Epub 2025 Dec 12.

Abstract

Background: Temporomandibular disorders (TMDs) and bruxism are the most common disorders affecting the oral and maxillofacial system. Patients with TMDs or bruxism frequently suffer from chronic head and neck pains (HNPs); however, the etiology between TMDs/bruxism and HNPs remains unclear.

Methods: We explore the association between TMDs/bruxism and HNPs with a bidirectional Mendelian randomization (MR) method with public online genome-wide association study (GWAS) data from the Integrative Epidemiology Unit (IEU) open GWAS project, FinnGen consortium and GWAS Catalog website. Inverse variance weighted (IVW) and other four statistical approaches were employed to investigate the associations. Furthermore, Cochran's Q, Mendelian randomization (MR)-Egger intercept test, MR pleiotropy residual sum and outlier test, and leave-one-out tests were conducted as sensitivity analyses to ensure the robustness of results. Multivariable MR (MVMR) analyses were adopted to validate the significant effects observed in the two-sample MR analyses while adjusting for potential confounders.

Results: Overall, our analysis revealed a reciprocal significant association between TMDs and neck/shoulder pain (NSP) in both forward (p = 0.023) and reverse (p = 0.004) analyses, which were corroborated by subsequent MVMR analyses adjusted for anxiety, body mass index (BMI) and sleeplessness. All results were confirmed robust under current sensitivity analysis.

Conclusions: These findings suggest a potential causal association between TMDs and HNPs. The bidirectional relationship highlight the importance of preventing TMDs and HNPs as a health strategy for mitigating each other's risks.

Keywords: Bruxism; Headache; Mendelian randomization; Pain; Temporomandibular disorders.

MeSH terms

  • Bruxism* / complications
  • Bruxism* / genetics
  • Female
  • Genome-Wide Association Study
  • Humans
  • Male
  • Mendelian Randomization Analysis
  • Neck Pain* / epidemiology
  • Neck Pain* / genetics
  • Temporomandibular Joint Disorders* / complications
  • Temporomandibular Joint Disorders* / genetics