A new genome-wide study, including one from the Kiel Pain Clinic, identifies genetic risk factors for cluster headache for the first time: The aim of the study was to collect data for the first meta-analysis of a genome-wide association study of cluster headache, to identify genetic risk variants and to gain biological insights into the cause of cluster headache.
A total of 4,777 patients (3,348 men and 1,429 women) with clinically diagnosed cluster headache were recruited from 10 European and 1 East Asian cohorts. Causal genes were prioritized using 5 complementary methods.
The estimated single nucleotide polymorphism (SNP)-based heritability of cluster headache was 14.5%. We identified nine independent signals at seven genome-wide significant loci in the primary meta-analysis and one additional locus in the trans-ethnic meta-analysis. The 20 genes prioritized as potentially causal for cluster headache showed enrichment in arteries and brain tissue. Cluster headache was genetically correlated with cigarette smoking, risk-taking behavior, attention deficit hyperactivity disorder (ADHD), depression, and musculoskeletal pain. Mendelian randomization analysis suggested a causal effect of cigarette smoking intensity on cluster headache. Three of the identified loci were shared with migraine.
This first meta-analysis of a genome-wide association study provides important insights into the biological basis of cluster headache.