Genetics of cluster headache

BackgroundCluster headache is the most severe primary headache disorder. A genetic basis has long been suggested by family and twin studies; however, little is understood about the genetic variants that contribute to cluster headache susceptibility.MethodsWe conducted a literature search of the MEDLINE database using the PubMed search engine to identify all human genetic studies for cluster headache. In this article we provide a review of those genetic studies, along with an overview of the pathophysiology of cluster headache and a brief review of migraine genetics, which have both been significant drivers of cluster headache candidate gene selection.ResultsThe investigation of cluster headache genetic etiology has been dominated by candidate gene studies. Candidate selection has largely been driven by the pathophysiology, such as the striking rhythmic nature of the attacks, which spurred close examination of the circadian rhythm genes CLOCK and HCRTR2. More recently, unbiased genetic approaches such as g...