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Objective: Ankylosing spondylitis (AS) is associated with a variety of gut microbiotas. We aim to analyze the causal relationship between the two at the genetic level. Methods: Mendelian randomization (MR) is a type of instrumental variables (IVs) analysis; MR follows the Mendelian genetic rule of "parental alleles are randomly assigned to offspring" and takes genetic variation as IVs to infer the causal association between exposure factors and study outcome in observational studies. Genome-wide association study (GWAS) summary data of AS were from the FinnGen consortium, and the gut microbiota (Bacteroides, Streptococcus, Proteobacteria, Lachnospiraceae) were from the MiBioGen consortium. The TwoSampleMR and MRPRESSO packages of the R were used to perform a two-sample MR study. Random-effects inverse variance weighted (IVW) was the main analysis method, and MR Egger, weighted median, simple mode, and weighted mode were used as supplementary methods. We examined heterogeneity and horizontal pleiotropy, and examined whether the analysis results were influenced by a single SNP. We applied radial variants of the IVW and MR-Egger model for the improved visualization of the causal estimate. We further examined the causal relationship between AS and gut microbiota, and the robustness of the analysis results. Finally, we performed maximum likelihood, penalized weighted median, and IVW (fixed effects) to further identify the potential causal association. Results: The random-effects IVW results showed that Bacteroides (p = 0.965, OR 95% confidence interval [CI] = 0.990 [0.621–1.579]), Streptococcus (p = 0.591, OR 95% CI = 1.120 [0.741–1.692]), Proteobacteria (p = 0.522, OR 95% CI = 1.160 [0.737–1.826]), and Lachnospiraceae (p = 0.717, OR 95% CI = 1.073 [0.732–1.574]) have no genetic causal relationship with AS. There was no heterogeneity, horizontal pleiotropy or outliers, and results were normally distributed. The MR analysis results were not driven by a single SNP. Conclusions: This study showed that Bacteroides, Streptococcus, Proteobacteria and Lachnospiraceae, four common gut microbiotas associated with AS, had no causal relationship with AS at the genetic level. This study makes a positive contribution to the genetics of AS, but the insufficient number of gut microbiota included is a limitation. [ABSTRACT FROM AUTHOR]

Based on previous observational studies, the causal association between circulating adiponectin (CA) levels and ankylosing spondylitis (AS) risk remains unclear. Therefore, this study aims to investigate whether CA levels are related to the risk of AS. We carried out a bidirectional two-sample Mendelian randomization (MR) analysis to examine the causal correlation between CA levels and AS via published genome-wide association study (GWAS) datasets. Single-nucleotide polymorphisms (SNPs) related to CA levels were derived from a large GWAS that included 39,883 individuals of European descent. SNPs related to AS were obtained from the FinnGen consortium (2252 cases and 227,338 controls). The random-effects inverse variance weighted (IVW) method was the primary method utilized in our research. We also used four complementary approaches to improve the dependability of this study (MR–Egger regression, Weighted median, Weighted mode, and Simple mode). Random-effects IVW (odds ratio [OR], 1.00; 95% confidence interval [CI], 0.79–1.27, p = 0.984) and four complementary methods all indicated that genetically predicted CA levels were not causally related to the risk of AS. In reverse MR analysis, there is little evidence to support the genetic causality between the risk of AS and CA levels. [ABSTRACT FROM AUTHOR]