N2′→P3′ Phosphoramidate Glycerol Nucleic Acid as a Potential Alternative Genetic System

N2′→P3′ Phosphoramidate Glycerol Nucleic Acid as a Potential Alternative Genetic Syste

Detailed information of instrumental variables used in MR analyses (Causal effects of PD on SS).

Detailed information of instrumental variables used in MR analyses (Causal effects of PD on SS).</p

A, B, and C depict the forest plot, leave-one-out analysis, and scatter plot, respectively, illustrating the relationship between Sjögren’s syndrome (SS) and Parkinson’s Disease (PD).

A, B, and C depict the forest plot, leave-one-out analysis, and scatter plot, respectively, illustrating the relationship between Sjögren’s syndrome (SS) and Parkinson’s Disease (PD).</p

The Mendelian randomization of Sjögren’s syndrome and Parkinson’s Disease.

The Mendelian randomization of Sjögren’s syndrome and Parkinson’s Disease.</p

An overview of this MR study design.

BackgroundPrevious 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.MethodsWe 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.ResultsThe 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.ConclusionThis 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.</div

Additional Mendelian randomization analysis by eliminating confounding factors.

Additional Mendelian randomization analysis by eliminating confounding factors.</p

Detailed information of instrumental variables used in MR analyses (Causal effects of SS on PD).

Detailed information of instrumental variables used in MR analyses (Causal effects of SS on PD).</p

The forest plot (A), leave-one-out analysis (B), and scatter plot (C) examine the impact of Parkinson’s Disease (PD) on Sjögren’s syndrome (SS).

The forest plot (A), leave-one-out analysis (B), and scatter plot (C) examine the impact of Parkinson’s Disease (PD) on Sjögren’s syndrome (SS).</p

DataSheet_1_Associations of the circulating levels of cytokines with risk of systemic sclerosis: a bidirectional Mendelian randomized study.pdf

ObjectiveSystemic sclerosis(SSc) remains unclear, studies suggest that inflammation may be linked to its pathogenesis. Hence, we conducted a bidirectional Mendelian randomization (MR) analysis to evaluate the association between cytokine and growth factor cycling levels and the risk of SSc onset.MethodsIn our study, the instrumental variables(IVs) for circulating cytokines were sourced from the genome-wide association study (GWAS) dataset of 8293 Finnish individuals. The SSc data comprised 302 cases and 213145 controls, and was included in the GWAS dataset. We employed four methods for the MR analysis: MR Egger, Inverse variance weighted (IVW), Weighted medium, and Weighted Mode, with IVW being the primary analytical method. Sensitivity analyses were performed using heterogeneity testing, horizontal pleiotropy testing, and the Leave One Out (LOO) method. We also conducted a reverse MR analysis to determine any reverse causal relationship between SSc and circulating cytokines.ResultsAfter Bonferroni correction, MR analysis revealed that the Interleukin-5 (IL-5) cycle level was associated with a reduced risk of SSc [odds ratio (OR)=0.48,95% confidence interval (CI): 0.27-0.84, P=0.01]. It also indicated that the Stem cell growth factor beta (SCGF-β) cycling level might elevate the risk of SSc (OR = 1.36, 95% CI: 1.01-1.83, P = 0.04). However, the reverse MR analysis did not establish a causal relationship between SSc and circulating cytokine levels. Additionally, sensitivity analysis outcomes affirm the reliability of our results.ConclusionOur MR study suggests potential causal relationships between IL-5, SCGF-β, and the risk of SSc. Further research is essential to determine how IL-5 and SCGF-β influence the development of SSc.</p

DataSheet_2_Associations of the circulating levels of cytokines with risk of systemic sclerosis: a bidirectional Mendelian randomized study.pdf

ObjectiveSystemic sclerosis(SSc) remains unclear, studies suggest that inflammation may be linked to its pathogenesis. Hence, we conducted a bidirectional Mendelian randomization (MR) analysis to evaluate the association between cytokine and growth factor cycling levels and the risk of SSc onset.MethodsIn our study, the instrumental variables(IVs) for circulating cytokines were sourced from the genome-wide association study (GWAS) dataset of 8293 Finnish individuals. The SSc data comprised 302 cases and 213145 controls, and was included in the GWAS dataset. We employed four methods for the MR analysis: MR Egger, Inverse variance weighted (IVW), Weighted medium, and Weighted Mode, with IVW being the primary analytical method. Sensitivity analyses were performed using heterogeneity testing, horizontal pleiotropy testing, and the Leave One Out (LOO) method. We also conducted a reverse MR analysis to determine any reverse causal relationship between SSc and circulating cytokines.ResultsAfter Bonferroni correction, MR analysis revealed that the Interleukin-5 (IL-5) cycle level was associated with a reduced risk of SSc [odds ratio (OR)=0.48,95% confidence interval (CI): 0.27-0.84, P=0.01]. It also indicated that the Stem cell growth factor beta (SCGF-β) cycling level might elevate the risk of SSc (OR = 1.36, 95% CI: 1.01-1.83, P = 0.04). However, the reverse MR analysis did not establish a causal relationship between SSc and circulating cytokine levels. Additionally, sensitivity analysis outcomes affirm the reliability of our results.ConclusionOur MR study suggests potential causal relationships between IL-5, SCGF-β, and the risk of SSc. Further research is essential to determine how IL-5 and SCGF-β influence the development of SSc.</p