{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:09Z","timestamp":1783036809233,"version":"3.54.6"},"reference-count":25,"publisher":"SAGE Publications","issue":"4-5","license":[{"start":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T00:00:00Z","timestamp":1634169600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cephalalgia"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Migraine is diagnosed using the extensively field-tested International Classification of Headache Disorders (ICHD-3) consensus criteria derived by the International Headache Society. To evaluate the criteria in respect to a measurable biomarker, we studied the relationship between the main ICHD-3 criteria and the polygenic risk score, a measure of common variant burden in migraine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used linear mixed models to study the correlation of ICHD-3 diagnostic criteria, underlying symptoms, and main diagnoses with the polygenic risk score of migraine in a cohort of 8602 individuals from the Finnish Migraine Genome Project.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Main diagnostic categories and all underlying diagnostic criteria formed a consistent continuum along the increasing polygenic burden. Polygenic risk was associated with the heterogeneous clinical picture starting from the non-migraine headache (mean 0.07; 95% CI 0.02\u20130.12; p\u2009=\u20090.008 compared to the non-headache group), to probable migraine (mean 0.13; 95% CI 0.08\u20130.18; p\u2009&lt;\u20090.001), migraine headache (mean 0.17; 95% CI 0.14\u20130.21; p\u2009&lt;\u20090.001) and migraine with typical visual aura (mean 0.29; 95% CI 0.26\u20130.33; p\u2009&lt;\u20090.001), all the way to the hemiplegic aura (mean 0.37; 95% CI 0.31\u20130.43; p\u2009&lt;\u20090.001). All individual ICHD-3 symptoms and the total number of reported symptoms, a surrogate of migraine complexity, demonstrated a clear inclination with an increasing polygenic risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The complex migraine phenotype progressively follows the polygenic burden from individuals with no headache to non-migrainous headache and up to patients with attacks manifesting all the features of the ICHD-3 headache and aura. Results provide further biological support for the ICHD-3 diagnostic criteria.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/03331024211045651","type":"journal-article","created":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T14:36:39Z","timestamp":1634222199000},"page":"345-356","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":16,"title":["Polygenic risk provides biological validity for the ICHD-3 criteria among Finnish migraine families"],"prefix":"10.1177","volume":"42","author":[{"given":"Paavo","family":"H\u00e4pp\u00f6l\u00e4","sequence":"first","affiliation":[{"name":"Institute for Molecular Medicine Finland FIMM, HiLIFE, University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Padhraig","family":"Gormley","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, Cambridge, MA, USA*"},{"name":"Department of Neurology, Massachusetts General Hospital, Boston, MA, USA"},{"name":"Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, and Harvard Medical School, Boston, MA, USA"},{"name":"Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA"},{"name":"The Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjo E","family":"Nuottamo","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine Finland FIMM, HiLIFE, University of Helsinki, Helsinki, Finland"},{"name":"Folkh\u00e4lsan Research Center, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ville","family":"Artto","sequence":"additional","affiliation":[{"name":"Department of Neurology, Helsinki University Hospital and University of Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marja-Liisa","family":"Sumelahti","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health, University of Tampere, Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markku","family":"Nissil\u00e4","sequence":"additional","affiliation":[{"name":"Terveystalo Clinical Research, Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Keski-S\u00e4ntti","sequence":"additional","affiliation":[{"name":"Terveystalo, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matti","family":"Ilmavirta","sequence":"additional","affiliation":[{"name":"Department of Neurology, Central Hospital Central Finland, Jyv\u00e4skyl\u00e4, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari A","family":"Kaunisto","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine Finland FIMM, HiLIFE, University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eija I","family":"H\u00e4m\u00e4l\u00e4inen","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine Finland FIMM, HiLIFE, University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuli","family":"Ripatti","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine Finland FIMM, HiLIFE, University of Helsinki, Helsinki, Finland"},{"name":"Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA"},{"name":"Department of Public Health, Clinicum, University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matti","family":"Pirinen","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine Finland FIMM, HiLIFE, University of Helsinki, Helsinki, Finland"},{"name":"Department of Public Health, Clinicum, University of Helsinki, Helsinki, Finland"},{"name":"Department of Mathematics and Statistics, University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maija","family":"Wessman","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine Finland FIMM, HiLIFE, University of Helsinki, Helsinki, Finland"},{"name":"Folkh\u00e4lsan Research Center, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aarno","family":"Palotie","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine Finland FIMM, HiLIFE, University of Helsinki, Helsinki, Finland"},{"name":"Department of Neurology, Massachusetts General Hospital, Boston, MA, USA"},{"name":"Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA"},{"name":"The Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, MA, USA"},{"name":"Analytic and Translational Genetics Unit, Department of Medicine, and Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikko","family":"Kallela","sequence":"additional","affiliation":[{"name":"Department of Neurology, Helsinki University Hospital and University of Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"International Headache Genetics Consortium (IHGC)","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2021,10,14]]},"reference":[{"key":"bibr1-03331024211045651","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1915327"},{"key":"bibr2-03331024211045651","first-page":"1","volume-title":"Cephalalgia","volume":"38","author":"Headache Classification Committee of the International Headache Society","year":"2018"},{"key":"bibr3-03331024211045651","first-page":"3","volume-title":"Headache classification and epidemiology","author":"Olesen J.","year":"1994"},{"key":"bibr4-03331024211045651","first-page":"9","volume-title":"The headaches","author":"Olesen J","year":"2006","edition":"3"},{"key":"bibr5-03331024211045651","first-page":"69","volume-title":"Headache classification and epidemiology","author":"Rasmussen BK","year":"1994"},{"key":"bibr6-03331024211045651","first-page":"77","volume-title":"Headache classification and epidemiology","author":"Dahl\u00f6f C","year":"1994"},{"key":"bibr7-03331024211045651","doi-asserted-by":"publisher","DOI":"10.1038\/nature08185"},{"key":"bibr8-03331024211045651","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.04.014"},{"key":"bibr9-03331024211045651","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-018-0856-0"},{"key":"bibr10-03331024211045651","doi-asserted-by":"publisher","DOI":"10.1046\/j.1468-1331.2001.00165.x"},{"key":"bibr11-03331024211045651","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2010.116"},{"key":"bibr12-03331024211045651","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2307"},{"key":"bibr13-03331024211045651","doi-asserted-by":"publisher","DOI":"10.1534\/g3.111.001198"},{"key":"bibr14-03331024211045651","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3598"},{"key":"bibr15-03331024211045651","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyx239"},{"key":"bibr16-03331024211045651","unstructured":"R Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. Open source, http:\/\/www.R-project.org\/."},{"key":"bibr17-03331024211045651","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.02.012"},{"key":"bibr18-03331024211045651","doi-asserted-by":"publisher","DOI":"10.1177\/0333102416678390"},{"key":"bibr19-03331024211045651","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32162-0"},{"key":"bibr20-03331024211045651","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-018-0418-5"},{"key":"bibr21-03331024211045651","doi-asserted-by":"publisher","DOI":"10.1017\/thg.2018.5"},{"key":"bibr22-03331024211045651","doi-asserted-by":"publisher","DOI":"10.1177\/0333102414547784"},{"key":"bibr23-03331024211045651","doi-asserted-by":"publisher","DOI":"10.1375\/twin.9.1.54"},{"key":"bibr24-03331024211045651","doi-asserted-by":"publisher","DOI":"10.1177\/0333102418761041"},{"key":"bibr25-03331024211045651","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyz254"}],"container-title":["Cephalalgia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/03331024211045651","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/03331024211045651","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/03331024211045651","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T14:49:16Z","timestamp":1777387756000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/03331024211045651"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,14]]},"references-count":25,"journal-issue":{"issue":"4-5","published-print":{"date-parts":[[2022,4]]}},"alternative-id":["10.1177\/03331024211045651"],"URL":"https:\/\/doi.org\/10.1177\/03331024211045651","relation":{},"ISSN":["0333-1024","1468-2982"],"issn-type":[{"value":"0333-1024","type":"print"},{"value":"1468-2982","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,14]]}}}