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Updated: Sep 9, 2025
A Proinflammatory, Degenerative Organ Culture Model to Simulate Early-Stage Intervertebral Disc Disease.
Published on: February 14, 2021
Exploring the causal relationships between spondyloarthritis/ankylosing spondylitis and intervertebral disc
Kexin Qin1,2, Xuejun Wang1,2, Guangzong Ren1,2
1Orthopedic Center, Changzhi People's Hospital, The Third Affiliated Hospital of Changzhi Medical College, No. 502, Changxing Middle Road, Luzhou District, Changzhi city, Shanxi Province, China.
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.
