PDF(Pubmed)
Abstract：
UNASSIGNED: Previous epidemiological studies have reported an association between Sjögren\'s syndrome (SS) and Parkinson\'s disease (PD); however, the causality and direction of this relationship remain unclear. In this study, we aimed to investigate the causal relationship between genetically determined SS and the risk of PD using bidirectional Mendelian randomization (MR).
UNASSIGNED: Summary statistics for Sjögren\'s syndrome used as exposure were obtained from the FinnGen database, comprising 1,290 cases and 213,145 controls. The outcome dataset for PD was derived from the United Kingdom Biobank database, including 6,998 cases and 415,466 controls. Various MR methods, such as inverse variance weighted (IVW), Mendelian randomization Egger regression (MR-Egger), weighted median (WM), simple mode, weighted mode, MR-pleiotropy residual sum and outlier (MR-PRESSO), and robust adjusted profile score (RAPS), were employed to investigate the causal effects of SS on PD. Instrumental variable strength evaluation and sensitivity analyses were conducted to ensure the reliability of the results. In addition, reverse MR analysis was performed to examine the causal effects of PD on SS.
UNASSIGNED: The WM, IVW, RAPS and MR-PRESSO methods demonstrated a significant association between genetically predicted SS and reduced risk of PD (odds ratio ORWM = 0.9988, ORIVW = 0.9987, ORRAPS = 0.9987, ORMR-PRESSO = 0.9987, respectively, P < 0.05). None of the MR analyses showed evidence of horizontal pleiotropy (P > 0.05) based on the MR-Egger and MR-PRESSO tests, and there was no statistical heterogeneity in the test results of the MR-Egger and IVW methods. The leave-one-out sensitivity analysis confirmed the robustness of the causal relationship between SS and PD. Furthermore, reverse MR analysis did not support any causal effects of PD on SS.
UNASSIGNED: Our MR study supports a potential causal association between SS and a reduced risk of PD. Further extensive clinical investigations and comprehensive fundamental research are warranted to elucidate the underlying mechanisms linking SS and PD.
UNASSIGNED: Summary statistics for Sjögren\'s syndrome used as exposure were obtained from the FinnGen database, comprising 1,290 cases and 213,145 controls. The outcome dataset for PD was derived from the United Kingdom Biobank database, including 6,998 cases and 415,466 controls. Various MR methods, such as inverse variance weighted (IVW), Mendelian randomization Egger regression (MR-Egger), weighted median (WM), simple mode, weighted mode, MR-pleiotropy residual sum and outlier (MR-PRESSO), and robust adjusted profile score (RAPS), were employed to investigate the causal effects of SS on PD. Instrumental variable strength evaluation and sensitivity analyses were conducted to ensure the reliability of the results. In addition, reverse MR analysis was performed to examine the causal effects of PD on SS.
UNASSIGNED: The WM, IVW, RAPS and MR-PRESSO methods demonstrated a significant association between genetically predicted SS and reduced risk of PD (odds ratio ORWM = 0.9988, ORIVW = 0.9987, ORRAPS = 0.9987, ORMR-PRESSO = 0.9987, respectively, P < 0.05). None of the MR analyses showed evidence of horizontal pleiotropy (P > 0.05) based on the MR-Egger and MR-PRESSO tests, and there was no statistical heterogeneity in the test results of the MR-Egger and IVW methods. The leave-one-out sensitivity analysis confirmed the robustness of the causal relationship between SS and PD. Furthermore, reverse MR analysis did not support any causal effects of PD on SS.
UNASSIGNED: Our MR study supports a potential causal association between SS and a reduced risk of PD. Further extensive clinical investigations and comprehensive fundamental research are warranted to elucidate the underlying mechanisms linking SS and PD.
摘要：
■以前的流行病学研究报道了干燥综合征（SS）和帕金森病（PD）之间的关联；然而，这种关系的因果关系和方向尚不清楚。在这项研究中,我们旨在通过双向孟德尔随机化(MR)研究遗传决定的SS与PD风险之间的因果关系.
■用作暴露的Sjögren综合征的汇总统计数据是从FinnGen数据库获得的，包括1,290例病例和213,145例对照。PD的结果数据集来自英国生物库数据库，包括6,998例病例和415,466例对照。各种MR方法，例如逆方差加权(IVW)，孟德尔随机化Egger回归(MR-Egger)，加权中位数(WM)，简单模式，加权模式，MR-多效性残差和和离群值(MR-PRESSO)，和稳健的调整后的配置文件得分(RAPS)，用于研究SS对PD的因果影响。进行了仪器变量强度评估和灵敏度分析，以确保结果的可靠性。此外,进行反向MR分析以检查PD对SS的因果影响.
■WM，IVW,RAPS和MR-PRESSO方法表明，遗传预测的SS与PD风险降低之间存在显着关联（比值比ORWM=0.9988，ORIVW=0.9987，ORRAPS=0.9987，ORMR-PRESSO=0.9987，P<0.05)。根据MR-Egger和MR-PRESSO测试，所有MR分析均未显示水平多效性证据（P>0.05），MR-Egger和IVW方法的测试结果没有统计学上的异质性。留一灵敏度分析证实了SS和PD之间因果关系的稳健性。此外，反向MR分析不支持PD对SS的任何因果影响.
■我们的MR研究支持SS与PD风险降低之间的潜在因果关系。需要进一步广泛的临床研究和全面的基础研究来阐明SS和PD之间的潜在机制。
■用作暴露的Sjögren综合征的汇总统计数据是从FinnGen数据库获得的，包括1,290例病例和213,145例对照。PD的结果数据集来自英国生物库数据库，包括6,998例病例和415,466例对照。各种MR方法，例如逆方差加权(IVW)，孟德尔随机化Egger回归(MR-Egger)，加权中位数(WM)，简单模式，加权模式，MR-多效性残差和和离群值(MR-PRESSO)，和稳健的调整后的配置文件得分(RAPS)，用于研究SS对PD的因果影响。进行了仪器变量强度评估和灵敏度分析，以确保结果的可靠性。此外,进行反向MR分析以检查PD对SS的因果影响.
■WM，IVW,RAPS和MR-PRESSO方法表明，遗传预测的SS与PD风险降低之间存在显着关联（比值比ORWM=0.9988，ORIVW=0.9987，ORRAPS=0.9987，ORMR-PRESSO=0.9987，P<0.05)。根据MR-Egger和MR-PRESSO测试，所有MR分析均未显示水平多效性证据（P>0.05），MR-Egger和IVW方法的测试结果没有统计学上的异质性。留一灵敏度分析证实了SS和PD之间因果关系的稳健性。此外，反向MR分析不支持PD对SS的任何因果影响.
■我们的MR研究支持SS与PD风险降低之间的潜在因果关系。需要进一步广泛的临床研究和全面的基础研究来阐明SS和PD之间的潜在机制。
