{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T08:39:21Z","timestamp":1792485561372,"version":"4.5.0"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,8,7]],"date-time":"2023-08-07T00:00:00Z","timestamp":1691366400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004590","name":"Central Norway Regional Health Authority","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004590","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI18\/01788"],"award-info":[{"award-number":["PI18\/01788"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI19\/01224"],"award-info":[{"award-number":["PI19\/01224"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI20\/00041"],"award-info":[{"award-number":["PI20\/00041"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["RF2009\u20101549619"],"award-info":[{"award-number":["RF2009\u20101549619"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001717","name":"Universiteit Leiden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001717","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2018\u201005973"],"award-info":[{"award-number":["2018\u201005973"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["076113"],"award-info":[{"award-number":["076113"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["085475"],"award-info":[{"award-number":["085475"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["090355"],"award-info":[{"award-number":["090355"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The objective of this study was to aggregate data for the first genomewide association study meta\u2010analysis of cluster headache, to identify genetic risk variants, and gain biological insights.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 4,777 cases (3,348 men and 1,429 women) with clinically diagnosed cluster headache were recruited from 10 European and 1 East Asian cohorts. We first performed an inverse\u2010variance genomewide association meta\u2010analysis of 4,043 cases and 21,729 controls of European ancestry. In a secondary trans\u2010ancestry meta\u2010analysis, we included 734 cases and 9,846 controls of East Asian ancestry. Candidate causal genes were prioritized by 5 complementary methods: expression quantitative trait loci, transcriptome\u2010wide association, fine\u2010mapping of causal gene sets, genetically driven DNA methylation, and effects on protein structure. Gene set and tissue enrichment analyses, genetic correlation, genetic risk score analysis, and Mendelian randomization were part of the downstream analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The estimated single nucleotide polymorphism (SNP)\u2010based heritability of cluster headache was 14.5%. We identified 9 independent signals in 7 genomewide significant loci in the primary meta\u2010analysis, and one additional locus in the trans\u2010ethnic meta\u2010analysis. Five of the loci were previously known. The 20 genes prioritized as potentially causal for cluster headache showed enrichment to artery and brain tissue. Cluster headache was genetically correlated with cigarette smoking, risk\u2010taking behavior, attention deficit hyperactivity disorder (ADHD), depression, and musculoskeletal pain. Mendelian randomization analysis indicated a causal effect of cigarette smoking intensity on cluster headache. Three of the identified loci were shared with migraine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>This first genomewide association study meta\u2010analysis gives clues to the biological basis of cluster headache and indicates that smoking is a causal risk factor. ANN NEUROL 2023;94:713\u2013726<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.26743","type":"journal-article","created":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T07:57:26Z","timestamp":1690185446000},"page":"713-726","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Cluster Headache Genomewide Association Study and Meta\u2010Analysis Identifies Eight Loci and Implicates Smoking as Causal Risk Factor"],"prefix":"10.1002","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4171-8919","authenticated-orcid":false,"given":"Bendik S.","family":"Winsvold","sequence":"first","affiliation":[{"name":"Department of Research and Innovation, Division of Clinical Neuroscience Oslo University Hospital  Oslo Norway"},{"name":"K. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences Norwegian University of Science and Technology (NTNU)  Trondheim Norway"},{"name":"Department of Neurology Oslo University Hospital  Oslo Norway"},{"name":"Norwegian Centre for Headache Research (NorHEAD), Department of Neuromedicine and Movement Science Norwegian University of Science and Technology (NTNU)  Trondheim Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5477-7232","authenticated-orcid":false,"given":"Aster V. E.","family":"Harder","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Leiden University Medical Center  Leiden The Netherlands"},{"name":"Department of Neurology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Ran","sequence":"additional","affiliation":[{"name":"Centre for Cluster Headache, Department of Neuroscience Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona A.","family":"Chalmer","sequence":"additional","affiliation":[{"name":"Department of Neurology, Danish Headache Center, Rigshospitalet\u2010Glostrup University of Copenhagen University Hospital  Glostrup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Carolina","family":"Dalmasso","sequence":"additional","affiliation":[{"name":"Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne University of Cologne  Cologne Germany"},{"name":"Neurosciences and Complex Systems Unit (EnyS), CONICET, Hospital El Cruce 'N. Kirchner' National University A. Jauretche (UNAJ)  Florencio Varela Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Egil","family":"Ferkingstad","sequence":"additional","affiliation":[{"name":"deCODE genetics\/Amgen Inc.  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