Additional file 4 of Transcriptome-wide association study identifies new susceptibility genes and pathways for spondyloarthritis

Additional file 4: Table S2 GO terms identified by Metascape enriched for Sp

Additional file 3 of Transcriptome-wide association study identifies new susceptibility genes and pathways for spondyloarthritis

Additional file 3: Table S1 Top genes selected by transcriptome-wide association study (TWAS) analysi

Additional file 1 of Transcriptome-wide association study identifies new susceptibility genes and pathways for spondyloarthritis

Additional file 1: Risk Loci in GWAS Dataset of SpA

Additional file 2 of Transcriptome-wide association study identifies new susceptibility genes and pathways for spondyloarthritis

Additional file 2: Quality Control Steps

The statistical power of IVW results in this study.

The statistical power of IVW results in this study.</p

Image_2_Causal associations between circulating inflammatory cytokines and blinding eye diseases: a bidirectional Mendelian randomization analysis.TIF

BackgroundPrevious studies have explored the associations between circulating inflammatory cytokines and blinding eye diseases, including glaucoma, cataract and macular degeneration. However, the causality of these associations remains controversial. This study employs a bidirectional Mendelian randomization (MR) study to investigate the causal relationships between 41 circulating inflammatory cytokines and these blinding eye diseases.MethodsSummary data for glaucoma, cataract, macular degeneration and 41 circulating inflammatory cytokines were publicly available. The inverse variance weighted (IVW) method was employed as the main analysis method. Additionally, various sensitivity tests, including MR–Egger regression, weighted median, weight mode, Cochran’s Q test, MR pleiotropy Residual Sum and Outlier test, and leave-one-out test, were conducted to evaluate sensitivity and stability of results.ResultsThe IVW analysis identified six circulating inflammatory cytokines causally associated with the risk of blinding eye diseases: Monokine induced by interferon-gamma (MIG) for glaucoma, interleukin-1 receptor antagonist (IL-1ra), IL-6, IL-10, and platelet derived growth factor BB (PDGFbb) for cataract, and MIG and hepatocyte growth factor (HGF) for macular degeneration. However, it is noteworthy that none of these associations remained significant after Bonferroni correction (p −04, 95% CI: 5.198 × 10−07 − 2.129 × 10−01, p = 0.0151).ConclusionThis study highlights the potential roles of specific inflammatory cytokines in the development of glaucoma, cataract and macular degeneration. Moreover, it suggests that VEGF is likely to be involved in cataract development downstream. These findings offer insights for early prevention and novel therapeutic strategies for these blinding eye diseases.</p

MR analysis results of the causal effect of RA on cataract and glaucoma in European and East Asian ancestry.

RA: rheumatoid arthritis; OR: odds ratio; CI: confidence interval; IVW: inverse variance weighted.</p

Table_1_Causal associations between circulating inflammatory cytokines and blinding eye diseases: a bidirectional Mendelian randomization analysis.XLSX

BackgroundPrevious studies have explored the associations between circulating inflammatory cytokines and blinding eye diseases, including glaucoma, cataract and macular degeneration. However, the causality of these associations remains controversial. This study employs a bidirectional Mendelian randomization (MR) study to investigate the causal relationships between 41 circulating inflammatory cytokines and these blinding eye diseases.MethodsSummary data for glaucoma, cataract, macular degeneration and 41 circulating inflammatory cytokines were publicly available. The inverse variance weighted (IVW) method was employed as the main analysis method. Additionally, various sensitivity tests, including MR–Egger regression, weighted median, weight mode, Cochran’s Q test, MR pleiotropy Residual Sum and Outlier test, and leave-one-out test, were conducted to evaluate sensitivity and stability of results.ResultsThe IVW analysis identified six circulating inflammatory cytokines causally associated with the risk of blinding eye diseases: Monokine induced by interferon-gamma (MIG) for glaucoma, interleukin-1 receptor antagonist (IL-1ra), IL-6, IL-10, and platelet derived growth factor BB (PDGFbb) for cataract, and MIG and hepatocyte growth factor (HGF) for macular degeneration. However, it is noteworthy that none of these associations remained significant after Bonferroni correction (p −04, 95% CI: 5.198 × 10−07 − 2.129 × 10−01, p = 0.0151).ConclusionThis study highlights the potential roles of specific inflammatory cytokines in the development of glaucoma, cataract and macular degeneration. Moreover, it suggests that VEGF is likely to be involved in cataract development downstream. These findings offer insights for early prevention and novel therapeutic strategies for these blinding eye diseases.</p

Detailed information on instrumental variables used in MR analyses.

SNP: single-nucleotide polymorphism; Beta: Estimate coefficient; P value: P value from GWAS; SE: standard error of coefficient estimate. (XLSX)</p

Scatter plots for the causal associations of RA with cataract and glaucoma.

The ordinate in scatter plots is the effect of the instrumental variables on the outcome, and the abscissa is the effect of the instrumental variables on the exposure. The causal effect of each method is represented by the slope of the line. (A) Scatter plot of RA on cataract in the European population; (B) Scatter plot of RA on glaucoma in the European population; (C) Scatter plot of cataract on RA in the European population; (D) Scatter plot of glaucoma on RA in the European population; (E) Scatter plot of RA on cataract in the East Asian population; (F) Scatter plot of RA on glaucoma in the East Asian population; (G) Scatter plot of cataract on RA in the East Asian population; (H) Scatter plot of glaucoma on RA in the East Asian population. RA: rheumatoid arthritis.</p