A new genome-wide study from the Kiel Pain Clinic, among others, identifies genetic risk factors for cluster headaches 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 headaches, to identify genetic risk variants and to gain biological insights into the cause of cluster headaches .
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 cohort. The causal genes were prioritized using 5 complementary methods.
The estimated single nucleotide polymorphism (SNP)-based heritability of cluster headache was 14.5%. We identified 9 independent signals in 7 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 clues to the biological basis of cluster headache.