Exploring the causal relationships between spondyloarthritis/ankylosing spondylitis and intervertebral disc degeneration: a bidirectional Mendelian randomization study

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In this study, we investigated the bidirectional causal relationship between spondyloarthritis (SpA)/ankylosing spondylitis (AS) and intervertebral disc degeneration (IVDD). Genome-wide association study (GWAS) statistics for SpA, AS, and IVDD were obtained exclusively from the FinnGen consortium. The instrumental variables (IVs) were identified under genome-wide significance thresholds ( P < 5 × 10 –8 ) with linkage disequilibrium clumping removed. An F-value exceeding 10 was deemed a robust association between IVs and exposure. The inverse-variance weighted (IVW) method was prioritized to infer causal relationships between SpA/AS and IVDD. To robustly evaluate reverse causality, reverse MR analyses were systematically implemented. Heterogeneity across single-nucleotide polymorphisms (SNPs) was quantified by conducting Cochran’s Q test and Rucker’s Q test; horizontal pleiotropy was assessed via MR-Egger intercept analysis. MR analyses demonstrated a significant causal effect of SpA on IVDD (IVW: OR = 1.04, 95% CI: 1.02–1.05, P adjust = 2.76E-05). Similarly, AS exhibited a robust causal association with IVDD (OR = 1.03, 95% CI: 1.02–1.04, P adjust = 2.08E-05). The reverse analyses revealed that IVDD significantly increased susceptibility to SpA (OR = 1.26, 95% CI: 1.14–1.40, P adjust = 7.07E-05) and AS (OR = 1.32, 95% CI: 1.14–1.52, P adjust = 8.10E-04). Neither significant heterogeneity nor horizontal pleiotropy was detected. SpA/AS significantly increased the risk of IVDD, whereas reverse MR analyses revealed that IVDD increased susceptibility to SpA/AS. Further experimental studies are required to confirm the bidirectional causal relationship between SpA/AS and IVDD.

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