Data_Sheet_1_The causal impact of saturated fatty acids on rheumatoid arthritis: a bidirectional Mendelian randomisation study.PDF

ObjectiveThe causal relationship between saturated fatty acids (SFAs) and rheumatoid arthritis (RA) remains poorly understood. This study aimed to determine whether SFAs are causally related to RA using Mendelian randomisation (MR) analyses.MethodsGenome-wide association study (GWAS) summary data for RA (ukb-d-M13_RHEUMA) and SFAs (met-d-SFA) were obtained from the Integrative Epidemiology Unit OpenGWAS database. A bidirectional MR analysis was performed using a suite of algorithms, namely the MR-Egger, weighted median, simple mode, weighted mode, and inverse-variance weighted (IVW) algorithms, all integrated using the “MR” function. The robustness of the MR findings was further evaluated through sensitivity analyses, including heterogeneity, horizontal pleiotropy, and leave-one-out tests.ResultsThe IVW algorithm in the forward MR analysis indicated a causal link between SFAs and RA (p = 0.025), identifying SFAs as a risk factor for RA (odds ratio = 1.001). Sensitivity analyses indicated no significant heterogeneity, horizontal pleiotropy, or severe bias, reinforcing the credibility of the forward MR results. However, the reverse MR analysis revealed that RA does not causally affect SFA levels (p = 0.195), and this finding was supported by corresponding sensitivity analyses.ConclusionThe findings of this study substantiate the positive causal effect of SFAs on the incidence of RA through bidirectional MR analysis, thereby offering a consequential direction for future research on the diagnosis and treatment of RA.</p

Table_1_The causal impact of saturated fatty acids on rheumatoid arthritis: a bidirectional Mendelian randomisation study.XLS

ObjectiveThe causal relationship between saturated fatty acids (SFAs) and rheumatoid arthritis (RA) remains poorly understood. This study aimed to determine whether SFAs are causally related to RA using Mendelian randomisation (MR) analyses.MethodsGenome-wide association study (GWAS) summary data for RA (ukb-d-M13_RHEUMA) and SFAs (met-d-SFA) were obtained from the Integrative Epidemiology Unit OpenGWAS database. A bidirectional MR analysis was performed using a suite of algorithms, namely the MR-Egger, weighted median, simple mode, weighted mode, and inverse-variance weighted (IVW) algorithms, all integrated using the “MR” function. The robustness of the MR findings was further evaluated through sensitivity analyses, including heterogeneity, horizontal pleiotropy, and leave-one-out tests.ResultsThe IVW algorithm in the forward MR analysis indicated a causal link between SFAs and RA (p = 0.025), identifying SFAs as a risk factor for RA (odds ratio = 1.001). Sensitivity analyses indicated no significant heterogeneity, horizontal pleiotropy, or severe bias, reinforcing the credibility of the forward MR results. However, the reverse MR analysis revealed that RA does not causally affect SFA levels (p = 0.195), and this finding was supported by corresponding sensitivity analyses.ConclusionThe findings of this study substantiate the positive causal effect of SFAs on the incidence of RA through bidirectional MR analysis, thereby offering a consequential direction for future research on the diagnosis and treatment of RA.</p

Table_2_The causal impact of saturated fatty acids on rheumatoid arthritis: a bidirectional Mendelian randomisation study.XLS

ObjectiveThe causal relationship between saturated fatty acids (SFAs) and rheumatoid arthritis (RA) remains poorly understood. This study aimed to determine whether SFAs are causally related to RA using Mendelian randomisation (MR) analyses.MethodsGenome-wide association study (GWAS) summary data for RA (ukb-d-M13_RHEUMA) and SFAs (met-d-SFA) were obtained from the Integrative Epidemiology Unit OpenGWAS database. A bidirectional MR analysis was performed using a suite of algorithms, namely the MR-Egger, weighted median, simple mode, weighted mode, and inverse-variance weighted (IVW) algorithms, all integrated using the “MR” function. The robustness of the MR findings was further evaluated through sensitivity analyses, including heterogeneity, horizontal pleiotropy, and leave-one-out tests.ResultsThe IVW algorithm in the forward MR analysis indicated a causal link between SFAs and RA (p = 0.025), identifying SFAs as a risk factor for RA (odds ratio = 1.001). Sensitivity analyses indicated no significant heterogeneity, horizontal pleiotropy, or severe bias, reinforcing the credibility of the forward MR results. However, the reverse MR analysis revealed that RA does not causally affect SFA levels (p = 0.195), and this finding was supported by corresponding sensitivity analyses.ConclusionThe findings of this study substantiate the positive causal effect of SFAs on the incidence of RA through bidirectional MR analysis, thereby offering a consequential direction for future research on the diagnosis and treatment of RA.</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

Table_1_Associations of the circulating levels of cytokines with risk of systemic sclerosis: a bidirectional Mendelian randomized study.doc

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

ObjectiveOsteoarthritis (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.MethodsWe 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.ResultsThe meta-analysis merger revealed a correlation between CX3CL1 cycle levels and increased OA risk (OR=1.070, 95% CI: 1.040-1.110; PConclusionOur 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.</p

DataSheet_1_The causal effect of cytokine cycling levels on osteoarthritis: a bidirectional Mendelian randomized study.pdf

ObjectiveOsteoarthritis (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.MethodsWe 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.ResultsThe meta-analysis merger revealed a correlation between CX3CL1 cycle levels and increased OA risk (OR=1.070, 95% CI: 1.040-1.110; PConclusionOur 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.</p

Table_1_The causal effect of cytokine cycling levels on osteoarthritis: a bidirectional Mendelian randomized study.xlsx

ObjectiveOsteoarthritis (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.MethodsWe 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.ResultsThe meta-analysis merger revealed a correlation between CX3CL1 cycle levels and increased OA risk (OR=1.070, 95% CI: 1.040-1.110; PConclusionOur 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.</p

Additional file 1 of Characterizations of the multi-kingdom gut microbiota in Chinese patients with gouty arthritis

Additional file 1: Table S1. Comparison of the gut bacteriome between GA patients and healthy controls at the phylum level. Table S2. Comparison of the gut bacteriome between GA patients and healthy controls at the genus level. Table S3. Comparison of the gut bacteriome between GA patients and healthy controls at the species level. Table S4. Comparison of the gut functional composition between GA patients and healthy conrols. Table S5. Comparison of the gut mycobiome between GA patients and healthy controls at the genus level. Table S6. Comparison of the gut virome between HC and GA subjects at the vOTUs level. Only vOTUs that differed in abundance between two groups are shown. Table S7. Detailed information of 42 KOs that differed in frequency between the GA-enriched and HC-enriched vOTUs