Genome-wide association susceptibility loci for cluster headache support a role for inflammation in the…

Meta-analysisThe journal of headache and pain· Aug 2026

Genome-wide association susceptibility loci for cluster headache support a role for inflammation in the pathophysiology.

Caroline Ran, Clémence Deborgies Sanches, Julia Swedblom … Andrea Carmine Belin

HeadacheMeta-analysisQ1IF 8.1

FHL5 gene variant linked to higher risk of cluster headache

Genome-wide association susceptibility loci for cluster headache support a role for inflammation in the pathophysiology.

Caroline Ran … Andrea Carmine Belin

The journal of headache and pain · Aug 2026 · Q1 in Neurology

Background

Recent genetic findings have broadened the perspectives of cluster headache pathophysiology.

Methods

Genetic loci were validated by means of a case-control study using TaqMan genotyping in 671 individuals, and a meta-analysis using previously genotyped data.

n = 671 individuals

Results

raises cluster headache risk

OR 1.29 (95% CI 1.09 to 1.52)

CI excludes the null - significant

More results

Genetic associations were found with functional variants in two genes; FHL5 and MERTK.

Methylation analysis further revealed altered methylation status of MERTK.

More results

Moreover, changes in relative gene expression were found for several candidate genes: a decrease in the mRNA expression of DUSP10 (P < 0.001), CAPN2 (P < 0.001), UFL1 (P < 0.001) and LRP1 (P = 0.007) in blood, and a decrease of CAPN2 (P < 0.001) as well as an increase in the mRNA expression of FTCDNL1/FONG (P = 0.004) in fibroblasts in CH vs. controls.

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Conclusion · 1 of 2

These results confirm the validity of seven candidate genes for cluster headache identified through GWAS.

Conclusion · 2 of 2

Furthermore, five of the candidate genes are abundantly expressed in both immune and blood cells, converge functionally on inflammatory signalling pathways and suggest a potential role for inflammasomes in cluster headache.

Genome-wide association susceptibility loci for cluster headache support a role for inflammation in the pathophysiology.

Genome-wide association susceptibility loci for cluster headache support a role for inflammation in the pathophysiology.

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