Department of Rheumatology, The First People's Hospital of Guiyang, Guiyang, Guizhou Province, China.
Department of Dermatology, The First People's Hospital of Guiyang, Guiyang, Guizhou Province, China.
PLoS One. 2024 Apr 3;19(4):e0298778. doi: 10.1371/journal.pone.0298778. eCollection 2024.
Previous observational studies have reported an association between Sjögren's syndrome (SS) and an increased risk of Parkinson's Disease (PD). However, the causal relationship between these conditions remains unclear. The objective of this study was to investigate the causal impact of SS on the risk of developing PD, utilizing the Mendelian randomization (MR) approach.
We conducted a bidirectional MR analysis using publicly available genome-wide association studies (GWAS) data. The primary analysis utilized the inverse-variance weighted (IVW) method. Complementary methods, such as MR-Egger regression, weighted mode, weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO), were utilized to identify and correct for the presence of horizontal pleiotropy.
The IVW MR analysis revealed no significant association between SS and PD (IVW: OR = 1.00, 95% CI = 0.94-1.07, P = 0.95). Likewise, the reverse MR analysis did not identify any significant causal relationship between PD and SS (IVW: OR = 0.98, 95% CI = 0.85-1.12, P = 0.73). The results from MR-Egger regression, weighted median, and weighted mode approaches were consistent with the IVW method. Sensitivity analyses suggested that horizontal pleiotropy is unlikely to introduce bias to the causal estimates.
This study does not provide evidence to support the assertion that SS has a conclusive impact on the risk of PD, which contradicts numerous existing observational reports. Further investigation is necessary to determine the possible mechanisms behind the associations observed in these observational studies.
先前的观察性研究报告称干燥综合征（SS）与帕金森病（PD）的风险增加之间存在关联。然而，这些疾病之间的因果关系尚不清楚。本研究旨在利用孟德尔随机化（MR）方法，研究 SS 对 PD 发病风险的因果影响。
我们使用公开的全基因组关联研究（GWAS）数据进行了双向 MR 分析。主要分析采用逆方差加权（IVW）法。互补方法，如 MR-Egger 回归、加权中位数、加权模式和 MR 偏倚剩余总和和异常值（MR-PRESSO），用于识别和纠正水平偏倚的存在。
IVW MR 分析显示 SS 与 PD 之间无显著关联（IVW：OR=1.00，95%CI=0.94-1.07，P=0.95）。同样，反向 MR 分析也未发现 PD 与 SS 之间存在任何显著的因果关系（IVW：OR=0.98，95%CI=0.85-1.12，P=0.73）。MR-Egger 回归、加权中位数和加权模式方法的结果与 IVW 方法一致。敏感性分析表明，水平偏倚不太可能对因果估计产生偏差。
本研究未提供证据支持 SS 对 PD 风险有明确影响的观点，这与许多现有的观察性报告相矛盾。需要进一步研究以确定这些观察性研究中观察到的关联背后的可能机制。
