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To date, treatment response has only been assessed by a candidate gene approach and no investigations into metabolic pathways have been performed. Our aim was to investigate the association between the polygenetic risk of cluster headache and treatment response to first\u2010line cluster headache treatments as well as known functional variants of <jats:italic>CYP3A4<\/jats:italic> and the response to verapamil. Further, it was aimed to replicate previous single nucleotide polymorphisms found to be associated with treatment response in cluster headache and\/or migraine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In, 508 cluster headache patients diagnosed according to the International Classification of Headache Disorders were genotyped and participated in a semi\u2010structured interview to evaluate treatment response. Polygenetic risk scores were calculated by the effect retrieved from a meta\u2010analysis of the latest two genome\u2010wide association studies on cluster headache.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Inferior treatment response to oxygen, triptans and verapamil is associated with chronicity of cluster headache were confirmed but no evidence was found that a response could be predicted by a high genetic risk of cluster headache. Likewise, verapamil response was not associated with functional variants of <jats:italic>CYP3A4<\/jats:italic>. No support of the genetic variants previously reported to be associated with treatment response to triptans or verapamil was found.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The clinically relevant variation in treatment response for cluster headache was not influenced by genetic factors in the present study.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.15736","type":"journal-article","created":{"date-parts":[[2023,2,11]],"date-time":"2023-02-11T13:54:50Z","timestamp":1676123690000},"page":"1425-1434","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Cluster headache polygenetic risk and known functional variants of <scp><i>CYP3A4<\/i><\/scp> are not associated with treatment response"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0125-6038","authenticated-orcid":false,"given":"Anja 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Rigshospitalet\u2010Glostrup  Glostrup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida","family":"Callesen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Danish Headache Centre Copenhagen University Hospital, Rigshospitalet\u2010Glostrup  Glostrup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4171-8919","authenticated-orcid":false,"given":"Bendik Slagsvold","family":"Winsvold","sequence":"additional","affiliation":[{"name":"Division of Clinical Neuroscience, Department of Research and Innovation Oslo University Hospital  Oslo Norway"},{"name":"Department of Neurology Oslo University Hospital  Oslo Norway"},{"name":"Institute of Clinical Medicine, Faculty of Medicine University of Oslo  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John\u2010Anker","family":"Zwart","sequence":"additional","affiliation":[{"name":"Division of Clinical 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