Genetics of Cluster Headache and Other Trigeminal Autonomic Cephalalgias

Cluster headache and other trigeminal autonomic cephalalgias (TACs) are rare and often severe primary headache disorders. Family and twin studies in cluster headache have demonstrated a clear genetic component, but the mode of transmission and the amount of heritability remain to be determined. A few familial cases of other TACs have been reported, but it is at present unknown to what extent these disorders are genetic. As a consequence, all genetic studies to date have focussed on the identification of genetic factors in cluster headache, foremost the testing of single nucleotide polymorphisms (SNPs) in candidate genes that were selected on presumed knowledge of the pathophysiology, but this did not result in any robust associations. More recently, the first genome-wide association study (GWAS) was conducted, albeit with limited success. Here we will (1) present current knowledge of the genetics of cluster headache and other TACs and (2) discuss factors potentially explaining why genetic studies were less successful in TACs than in migraine. Learning from the past, genetic studies in cluster headache and other TACs may hopefully be more fruitful in the future.