Sjögren's syndrome and Parkinson's Disease: A bidirectional two-sample Mendelian randomization study

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.