Affiliation:
1. Department of Otolaryngology‐Head and Neck Surgery, Xiangya Hospital Central South University Changsha Hunan China
2. Otolaryngology Major Disease Research Key Laboratory of Hunan Province Changsha Hunan China
3. Clinical Research Center for Pharyngolaryngeal Diseases and Voice Disorders in Hunan Province Changsha Hunan China
4. National Clinical Research Center for Geriatric Disorders (Xiangya Hospital) Changsha Hunan China
Abstract
AbstractBackground and ObjectivePrevious studies suggest interaction between periodontitis and thyroid function, while the causality has not yet been established. We applied the Mendelian randomization (MR) method to assess bidirectional causal association between periodontitis and thyroid‐related traits, including free thyroxine (FT4), thyroid stimulating hormone (TSH), hypothyroidism, hyperthyroidism and autoimmune thyroid disease (AITD).MethodsGenetic instruments were extracted from large‐scale genome‐wide association studies on normal‐range FT4 (N = 49 269) and TSH (N = 54 288) levels, TSH in full range (N = 119 715); hypothyroidism (discovery/replication cohorts: N = 53 423/334 316), hyperthyroidism (discovery/replication cohorts: N = 51 823/257 552), AITD (N = 755 406) and periodontitis (N = 45 563). Here, the inverse variance weighted (IVW) method was applied as the primary analysis, and robustness of results were assessed by several pleiotropic‐robust methods. Results were adjusted for Bonferroni correction thresholds with significant p < .004 (0.05/13) and suggestive p between .004 and .05.ResultsThe IVW analysis revealed a suggestively causal linkage between genetic predisposition to periodontitis and the increased risk of hypothyroidism (discovery cohort: odds ratio [OR] = 1.24, 95% confidence interval [CI] = 1.05–1.46, p = .012; replication cohort: OR = 1.06, 95% CI = 1.01–1.11, p = .011). No evidence was found for supporting the impact of periodontitis on hyperthyroidism and AITD risks (associated p ≥ .209), as well as thyroid‐related traits on periodontitis risk (associated p ≥ .105). These findings were robust and consistent through sensitivity analysis with other MR models.ConclusionThis bidirectional MR reveals periodontitis should not be attributed to variations in thyroid function but it has potential causal effect on hypothyroidism risk, which provides a better understanding of the relationship between periodontitis and thyroid function, and potential evidence for the clinical intervention of hypothyroidism. Further investigations are warranted to elucidate the nature and underlying mechanisms of this finding.
Funder
National Natural Science Foundation of China