ArticleMetabolites2026
Causal Effects of Plasma Metabolites on Intervertebral Disc Degeneration and Low Back Pain: A Mendelian Randomization Study.
Article in Metabolites, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundMetabolic disturbances have been implicated in intervertebral disc degeneration (IVDD) and low back pain, but the contribution of circulating metabolites remains uncertain.
objectivesWe examined associations of genetically proxied plasma metabolites and metabolite ratios with IVDD outcomes defined at different anatomical locations and with a related pain phenotype.
methodsSummary statistics for metabolite exposures were obtained from the Canadian Longitudinal Study on Ageing (CLSA) plasma metabolome genome-wide association study (GWAS). The outcomes were Intervertebral Disc Degeneration of Cervical Spine (IVDD_Cervical), Intervertebral Disc Degeneration of Thoracic, Thoracolumbar, and Lumbosacral Spine (IVDD_TTL), and Low Back Pain (Pain_Lowback). IVDD_Cervical and IVDD_TTL represented IVDD outcomes defined at different anatomical locations of the spine, whereas Pain_Lowback was analysed separately as an IVDD-related pain phenotype. One genome-wide significant sentinel single-nucleotide variant (SNV) was used for each exposure, and Mendelian randomization (MR) estimates were calculated with the Wald ratio. The within-outcome Bonferroni threshold was 6.25 × 10
resultsEighty metabolites and metabolite ratios were evaluated. Two associations were significant, both for IVDD_TTL. Higher genetically proxied dimethylarginine (SDMA + ADMA), mapped to DDAH1, was associated with lower IVDD_TTL risk (odds ratio [OR] = 0.80; 95% confidence interval [CI]: 0.72-0.90;
conclusionsThe results highlight DDAH1-linked methylarginine metabolism and LDHA-linked glycolytic and lactate-related biology as candidate pathways for IVDD_TTL. Findings for IVDD_Cervical, Pain_Lowback, and cross-outcome overlap remain exploratory.
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