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Background <p>In this study, we investigated the bidirectional causal relationship between spondyloarthritis (SpA)/ankylosing spondylitis (AS) and intervertebral disc degeneration (IVDD).</p> Methods <p>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 (<i>P</i> &lt; 5 × 10<sup>–8</sup>) 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.</p> Results <p>MR analyses demonstrated a significant causal effect of SpA on IVDD (IVW: OR = 1.04, 95% CI: 1.02–1.05, <i>P</i><sub>adjust</sub> = 2.76E-05). Similarly, AS exhibited a robust causal association with IVDD (OR = 1.03, 95% CI: 1.02–1.04, <i>P</i><sub>adjust</sub> = 2.08E-05). The reverse analyses revealed that IVDD significantly increased susceptibility to SpA (OR = 1.26, 95% CI: 1.14–1.40, <i>P</i><sub>adjust</sub> = 7.07E-05) and AS (OR = 1.32, 95% CI: 1.14–1.52, <i>P</i><sub>adjust</sub> = 8.10E-04). Neither significant heterogeneity nor horizontal pleiotropy was detected.</p> Conclusions <p>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.</p>

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

  • 期刊论文

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  • 发表日期：

    2025年8月30日

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  • Kexin Qin,
  • Xuejun Wang,
  • Guangzong Ren,
  • Kai Zhang,
  • Xiaochun Yang,
  • Zunpeng Liu

摘要

Background

In this study, we investigated the bidirectional causal relationship between spondyloarthritis (SpA)/ankylosing spondylitis (AS) and intervertebral disc degeneration (IVDD).

Methods

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.

Results

MR analyses demonstrated a significant causal effect of SpA on IVDD (IVW: OR = 1.04, 95% CI: 1.02–1.05, Padjust = 2.76E-05). Similarly, AS exhibited a robust causal association with IVDD (OR = 1.03, 95% CI: 1.02–1.04, Padjust = 2.08E-05). The reverse analyses revealed that IVDD significantly increased susceptibility to SpA (OR = 1.26, 95% CI: 1.14–1.40, Padjust = 7.07E-05) and AS (OR = 1.32, 95% CI: 1.14–1.52, Padjust = 8.10E-04). Neither significant heterogeneity nor horizontal pleiotropy was detected.

Conclusions

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.