ArticleJournal of pain research2026
Bidirectional Mendelian Randomization Analysis of 338 Cerebrospinal-Fluid Metabolites and Cluster-Headache Risk.
Article in Journal of pain research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
1 citing paper in PubMed.
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Cluster headache (CH) is a rare but highly disabling primary headache disorder characterized by severe unilateral attacks and autonomic symptoms. The metabolic mechanisms underlying CH remain poorly understood. Objective: To investigate the potential causal effects of cerebrospinal fluid (CSF) metabolite levels on CH risk, and to explore possible reverse causal effects of CH on CSF metabolites, using a bidirectional Mendelian randomization (MR) approach. Methods: We performed a bidirectional two-sample Mendelian randomization (MR) analysis integrating genome-wide association study (GWAS) data for 338 cerebrospinal fluid (CSF) metabolites and CH (1,833 cases and 498,515 controls from FinnGen release 12). Genetic instruments were selected at P < 1×10 Results: In the forward MR analysis, 11 CSF metabolites were significantly associated with CH risk (P<0.05). The strongest associations were observed for orotate (β = 0.53, 95% CI: 0.23-0.82, P = 0.0006), betaine (β = 0.47, 95% CI: 0.16-0.79, P = 0.0035), and 5-oxoproline (β = 0.57, 95% CI: 0.17-0.97, P = 0.0053). In the reverse MR analysis, eight metabolites, including lysine (β = 0.015, P = 0.029) and kynurenine (β = 0.025, P = 0.020), were nominally associated with genetic liability to CH. Sensitivity analyses showed no evidence of directional pleiotropy or heterogeneity (all P > 0.05). Conclusion: This bidirectional MR study provides the first genetic evidence linking central metabolic alterations to CH susceptibility. While these results highlight potential metabolic biomarkers and mechanistic pathways, the findings remain preliminary due to modest statistical power and should be replicated in larger and ethnically diverse cohorts.
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