Zeng Shiya, Tan Yanyue, Cao Zhiwei, Zheng Yunhao, Liu Tiqian, Deng Yifei, Xiong Xin
State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People's Republic of China.
Department of Nursing, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People's Republic of China.
J Pain Res. 2024 Oct 26;17:3487-3500. doi: 10.2147/JPR.S489583. eCollection 2024.
Growing researches explore vitamin D's role in temporomandibular disorders (TMDs), but the link between vitamin D and TMDs remains debated. To clarify the causal relationship, we conducted a Mendelian randomization (MR) analysis using data from genome-wide association studies (GWAS).
The GWAS dataset of vitamin D (GWAS ID: ukb-d-30890_irnt; sample size: 329247) was obtained from the IEU Open GWAS project. And that of TMDs (GWAS ID: finn-b-TEMPORO; sample size: 134280), initiated on August 25th, 2017 and publicly released on December 18th, 2023, was extracted from the FinnGen dataset, whose cases were diagnosed based on the revised International Classification of Diseases, 10th Edition (ICD-10) code K07.6. Both datasets were obtained from the European population. According to three assumptions of MR analysis, a bi-directional MR analysis was performed to measure the causal relationship, with Inverse variance weighted (IVW) as the primary method and MR Egger and Weighted median as supplement. Moreover, diverse sensitivity analyses, including Cochran's Q test, MR Egger intercept, Mendelian randomized polymorphism RESidual Sum and Outlier (MR-PRESSO), and leave-one-out analysis, were used to verify the stability of the findings.
The MR analysis supported causal effects of vitamin D levels on TMDs risks within the European population using IVW method [odds ratio = 1.316; 95% confidence interval = 1.086 to 1.595; P = 0.005], supported by MR Egger and Weighted median. While there was no indication that TMDs have a direct impact on vitamin D levels [β: -0.00738, standard error = 0.00665; P = 0.568].
The study revealed that within the European population higher levels of vitamin D led to higher risks of developing temporomandibular disorders, but found no obvious evidence that TMDs are causally associated with vitamin D. The conclusion should be cautiously interpreted, given the selection bias of TMDs patients sample.
越来越多的研究探讨维生素D在颞下颌关节紊乱病（TMDs）中的作用，但维生素D与TMDs之间的联系仍存在争议。为了阐明因果关系，我们使用全基因组关联研究（GWAS）的数据进行了孟德尔随机化（MR）分析。
维生素D的GWAS数据集（GWAS ID：ukb-d-30890_irnt；样本量：329247）来自IEU Open GWAS项目。而TMDs的数据集（GWAS ID：finn-b-TEMPORO；样本量：134280）于2017年8月25日启动，并于2023年12月18日公开发布，从FinnGen数据集中提取，其病例根据修订后的第10版国际疾病分类（ICD-10）代码K07.6进行诊断。两个数据集均来自欧洲人群。根据MR分析的三个假设，进行了双向MR分析以测量因果关系，以逆方差加权（IVW）为主要方法，MR Egger和加权中位数为补充。此外，还使用了多种敏感性分析，包括 Cochr an's Q检验、MR Egger截距、孟德尔随机化多态性残差和异常值（MR-PRESSO）以及留一法分析，以验证研究结果的稳定性。
MR分析支持使用IVW方法在欧洲人群中维生素D水平对TMDs风险的因果效应[优势比 = 1.316；95%置信区间 = 1.086至1.595；P = 0.005]，MR Egger和加权中位数也支持这一结果。而没有迹象表明TMDs对维生素D水平有直接影响[β：-0.00738，标准误 = 0.00665；P = 0.568]。
该研究表明，在欧洲人群中，较高水平的维生素D会导致患颞下颌关节紊乱病的风险增加，但没有发现明显证据表明TMDs与维生素D存在因果关系。鉴于TMDs患者样本的选择偏倚，该结论应谨慎解读。
