Fig 1.
The flowchart of MR analyses between AS and GM.
GWAS, genome wide association study; GM, gut microbiota; AS, ankylosing spondylitis; IVs, instrumental variables; SNPs, single nucleotide polymorphisms; MR, mendelian randomization; IVW, inverse variance weighted; MR-PRESSO, mendelian randomization-pleiotropy residual sum and outlier.
Fig 2.
Diagrams illustrating associations for mediation MR analysis.
Table 1.
GWAS data information for inflammatory cytokines.
Fig 3.
Suggestively causal effects of GM on AS.
P_heterogeneity represents the p-value obtained by Cochran’s Q test. P_intercept indicates p-value obtained by MR-Egger intercept test. NA stands for anomaly estimate. The forest plot represents the pooled odds ratio and 95% confidence interval under IVW, weighted median, and MR-Egger methods. N. SNPs represents the final number of SNPs retained for MR analyses. AS, ankylosing spondylitis; IVW, inverse variance weighted; OR, odds ratio; CI, confidence interval.
Fig 4.
Scatter plots for suggestively causal effects of GM on AS.
The 95%CI of odd ratio (OR) for each IV is presented by vertical and horizontal lines. The slope of the lines represents estimated causal effect of MR methods. Light blue lines represent estimations with IVW method. Blue lines represent estimations with MR-Egger method. Green lines represent estimations with weighted median method. Light green lines represent estimations with simple mode method. Red lines represent estimations with weighted mode method. (a): Scatter plot of 5 MR methods for causal effect of Actinobacteria class on AS. (b): Scatter plot of 5 MR methods for causal effect of Lactobacillaceae family on AS. (c): Scatter plot of 5 MR methods for causal effect of Rikenellaceae family on AS. (d): Scatter plot of 5 MR methods for causal effect of Howardella genus on AS. (e): Scatter plot of 5 MR methods for causal effect of Ruminococcaceae_NK4A214_group genus on AS. MR, mendelian randomization. GM, gut microbiota; AS, ankylosing spondylitis; SNPs, single nucleotide polymorphisms.
Fig 5.
Results of leave-one-out analysis for suggestively causal effects of GM on AS.
The figures showed the MR analysis results after phasing out single SNP one by one. Red lines represent estimations from IVW test. (a): Forest plots for Actinobacteria class on AS. (b): Forest plots for Lactobacillaceae family on AS. (c): Forest plots for Rikenellaceae family on AS. (d): Forest plots for causal effect of Howardella genus on AS. (e): Forest plots for causal effect of Ruminococcaceae_NK4A214_group genus on AS. AS, ankylosing spondylitis.
Fig 6.
P_heterogeneity represents the p-value obtained by Cochran’s Q test. P_intercept indicates p-value obtained by MR-Egger intercept test. The forest plot represents the pooled odds ratio and 95% confidence interval under the IVW, Weighted median, and MR-Egger methods. N. SNPs represents the final number of SNPs retained for MR analyses. AS, ankylosing spondylitis; IVW, inverse variance weighted; OR, odds ratio; CI, confidence interval.
Table 2.
Causal effects of Actinobacteria class on IL23 and IFN-γ.
Fig 7.
The internal relationship between GM and AS.
GM, gut microbiota; AS, ankylosing spondylitis.