颞下颌关节紊乱与脑影像衍生表型之间的关联。

Associations Between Temporomandibular Disorders and Brain Imaging-Derived Phenotypes.

机构信息

Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, Testing Center of Stomatology, Xi'an Jiaotong University College of Stomatology, Xi'an, Shaanxi, China.

出版信息

Int Dent J. 2024 Aug;74(4):784-793. doi: 10.1016/j.identj.2024.01.008. Epub 2024 Feb 15.

DOI:10.1016/j.identj.2024.01.008

PMID:38365503

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11287171/

Abstract

OBJECTIVE

Temporomandibular disorders (TMD) affect the temporomandibular joint and associated structures. Despite its prevalence and impact on quality of life, the underlying mechanisms of TMD remain unclear. Magnetic resonance imaging studies suggest brain abnormalities in patients with TMD. However, these lines of evidence are essentially observational and cannot infer a causal relationship. This study employs Mendelian randomisation (MR) to probe causal relationships between TMD and brain changes.

METHODS

Genome-wide association study (GWAS) summary statistics for TMD were collected, along with brain imaging-derived phenotypes (IDPs). Instrumental variables were selected from the GWAS summary statistics and used in bidirectional 2-sample MR analyses. The inverse-variance weighted analysis was chosen as the primary method. In addition, false discovery rate (FDR) correction of P value was used.

RESULTS

Eleven IDPs related to brain imaging alterations showed significant causal associations with TMD (P-FDR < .05), validated through sensitivity analysis. In forward MR, the mean thickness of left caudal middle frontal gyrus (OR, 0.76; 95% CI, 0.67-0.87; P-FDR = 1.15 × 10) and the volume of right superior frontal gyrus (OR, 1.24; 95% CI, 1.10-1.39; P-FDR = 2.26 × 10) exerted significant causal effects on TMD. In the reverse MR analysis, TMD exerted a significant causal effect on 9 IDPs, including the mean thickness of the left medial orbitofrontal cortex (β = -0.10; 95% CI, -0.13 to -0.08; P-FDR = 2.06 × 10), the volume of the left magnocellular nucleus (β = -0.15; 95% CI, -0.22 to -0.09; P-FDR = 3.26 × 10), the mean intensity of the right inferior-lateral ventricle (β = -0.09; 95% CI, -0.14 to -0.04; P-FDR = 2.23 × 10), the volume of grey matter in the anterior division of the left superior temporal gyrus (β = 0.09; 95% CI, 0.04-0.14; P-FDR = 1.69 × 10), and so forth.

CONCLUSIONS

This study provides genetic evidence supporting the bidirectional causal associations between TMD and brain IDPs, shedding light on potential neurobiological mechanisms underlying TMD development and its relationship with brain structure.

摘要

目的

颞下颌关节紊乱（TMD）影响颞下颌关节及其相关结构。尽管 TMD 患病率高且对生活质量有影响，但 TMD 的潜在机制仍不清楚。磁共振成像研究表明 TMD 患者存在大脑异常。然而，这些证据主要是观察性的，并不能推断出因果关系。本研究采用孟德尔随机化（MR）来探究 TMD 与大脑变化之间的因果关系。

方法

收集了 TMD 的全基因组关联研究（GWAS）汇总统计数据，以及大脑成像衍生表型（IDPs）。从 GWAS 汇总统计数据中选择了工具变量，并用于双向 2 样本 MR 分析。选择逆方差加权分析作为主要方法。此外，还使用了错误发现率（FDR）校正 P 值。

结果

11 个与大脑成像改变相关的 IDP 与 TMD 存在显著的因果关联（P-FDR <.05），通过敏感性分析得到验证。在正向 MR 中，左侧尾状额中回的平均厚度（OR，0.76；95%CI，0.67-0.87；P-FDR = 1.15 × 10）和右侧额上回的体积（OR，1.24；95%CI，1.10-1.39；P-FDR = 2.26 × 10）对 TMD 有显著的因果作用。在反向 MR 分析中，TMD 对 9 个 IDP 产生了显著的因果效应，包括左侧内侧眶额皮质的平均厚度（β=-0.10；95%CI，-0.13 至 -0.08；P-FDR = 2.06 × 10）、左侧大细胞核的体积（β=-0.15；95%CI，-0.22 至 -0.09；P-FDR = 3.26 × 10）、右侧下外侧脑室的平均强度（β=-0.09；95%CI，-0.14 至 -0.04；P-FDR = 2.23 × 10）、左侧上颞叶前部分的灰质体积（β=0.09；95%CI，0.04-0.14；P-FDR = 1.69 × 10）等。