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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

The causal effect of cytokine cycling levels on osteoarthritis: a bidirectional Mendelian randomized study.

Objective: Osteoarthritis (OA) is the most prevalent joint disease globally, serving as a primary cause of pain and disability. However, the pathological processes underlying OA remain incompletely understood. Several studies have noted an association between cytokines and OA, yet the causal link between them remains ambiguous. This study aims to identify cytokines potentially causally related to OA using Mendelian randomization (MR) analysis, informing early clinical diagnosis and treatment decisions. Methods: We conducted a genome-wide association study (GWAS) on 12 OA traits involving 177,517 cases and 649,173 controls from 9 international cohorts. For discovery MR analysis, we used 103 cytokines from two European populations as instrumental variables (IVs). Concurrently, another European population OA GWAS database (36,185 cases and 135,185 controls) was used to replicate MR analysis, employing the inverse variance weighted (IVW) method as the primary analytic approach. Additional methods tested included MR Egger, Weighted median, and Weighted mode. We merged the MR findings through meta-analysis. Heterogeneity testing, level pleiotropy testing (MR Egger intercept test and MRPRESSO), and sensitivity analysis via Leave One Out (LOO) were conducted to verify result robustness. Lastly, reverse MR analysis was performed. Results: The meta-analysis merger revealed a correlation between CX3CL1 cycle levels and increased OA risk (OR=1.070, 95% CI: 1.040-1.110; P<0.010). We also observed associations between MCP4 (OR=0.930, 95% CI: 0.890-0.970; P<0.010) and CCL25 (OR=0.930, 95% CI: 0.890-0.970; P<0.010) with reduced OA risk. The sensitivity analysis results corroborate the robustness of these findings. Conclusion: Our MR analysis indicates a potential causal relationship between CX3CL1, MCP4, CCL25, and OA risk changes. Further research is warranted to explore the influence of cytokines on OA development.