{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T23:19:33Z","timestamp":1784762373911,"version":"3.55.0"},"reference-count":30,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T00:00:00Z","timestamp":1736985600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000133","name":"Agency for Healthcare Research and Quality","doi-asserted-by":"publisher","award":["R01HS024057"],"award-info":[{"award-number":["R01HS024057"]}],"id":[{"id":"10.13039\/100000133","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Migraine is a common neurological disorder with highly variable characteristics. While genome-wide association studies have identified genetic risk factors that implicate underlying pathways, the influence of genetic susceptibility on disease characteristics or treatment response is incompletely understood. We examined the relationships between a previously developed standardized integrative migraine polygenic genetic risk score (PRS) and migraine characteristics in a real-world, treated patient cohort. Methods: This retrospective cohort study used covariate-adjusted regression to comprehensively evaluate associations between the PRS and clinical characteristics in 1653 treated migraine cases with European ancestry at baseline and, in 800 cases, after one year. Cases were deeply phenotyped by neurologists during extensive interviews, using structured clinical documentation tools to record ~200 discrete data elements. Results: In treated patients, higher standardized PRS showed associations with two common migraine symptoms: photophobia (odds ratio [confidence interval]: 1.33 [1.13\u20131.56], p = 0.001) and stabbing pain (1.21 [1.08\u20131.36], p = 0.001]; both retained significance at Q = 0.05. Associations with phonophobia, nausea, emesis, and unilateral headache had similar effect sizes but did not survive correction for multiple tests. In this population, the PRS was not associated with other symptoms of migraine attacks, objective measures of migraine disability, frequency, severity, average duration, time-to-peak intensity of migraine attacks, chronification, emergency department visits, triptan responsiveness, or changes at follow-up. Conclusions: In treated patients, genetic risk was associated with common migraine symptoms but not with the severity of migraine characteristics or treatment outcomes. This suggests that in treated patients, other genetic and non-genetic factors influence migraine symptom severity and disease course more strongly than genetic susceptibility.<\/jats:p>","DOI":"10.3390\/jcm14020536","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T06:46:10Z","timestamp":1737009970000},"page":"536","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Migraine Genetic Susceptibility Does Not Strongly Influence Migraine Characteristics and Outcomes in a Treated, Real-World, Community Cohort"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5491-7242","authenticated-orcid":false,"given":"Bruce A.","family":"Chase","sequence":"first","affiliation":[{"name":"Department of Information Technology, Endeavor Health, Skokie, IL 60077, USA"},{"name":"Pritzker School of Medicine, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Frigerio","sequence":"additional","affiliation":[{"name":"Pritzker School of Medicine, Chicago, IL 60637, USA"},{"name":"Research Institute, Endeavor Health, Evanston, IL 60201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Rubin","sequence":"additional","affiliation":[{"name":"Department of Neurology, Endeavor Health, Evanston, IL 60201, USA"},{"name":"University of Chicago Pritzker School of Medicine, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Semenov","sequence":"additional","affiliation":[{"name":"Pritzker School of Medicine, Chicago, IL 60637, USA"},{"name":"Department of Neurology, Endeavor Health, Evanston, IL 60201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5207-6758","authenticated-orcid":false,"given":"Steven","family":"Meyers","sequence":"additional","affiliation":[{"name":"Pritzker School of Medicine, Chicago, IL 60637, USA"},{"name":"Department of Neurology, Endeavor Health, Evanston, IL 60201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Mark","sequence":"additional","affiliation":[{"name":"Department of Neurology, Endeavor Health, Evanston, IL 60201, USA"},{"name":"University of Chicago Pritzker School of Medicine, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Freedom","sequence":"additional","affiliation":[{"name":"Pritzker School of Medicine, Chicago, IL 60637, USA"},{"name":"Department of Neurology, Endeavor Health, Evanston, IL 60201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Revital","family":"Marcus","sequence":"additional","affiliation":[{"name":"Department of Neurology, Endeavor Health, Evanston, IL 60201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rima","family":"Dafer","sequence":"additional","affiliation":[{"name":"Department of Neurology, Endeavor Health, Evanston, IL 60201, USA"},{"name":"Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wei","sequence":"additional","affiliation":[{"name":"Center for Individualized Medicine, Endeavor Health, Evanston, IL 60201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqun L.","family":"Zheng","sequence":"additional","affiliation":[{"name":"Center for Individualized Medicine, Endeavor Health, Evanston, IL 60201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1343-8752","authenticated-orcid":false,"given":"Jianfeng","family":"Xu","sequence":"additional","affiliation":[{"name":"Center for Individualized Medicine, Endeavor Health, Evanston, IL 60201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0042-1358","authenticated-orcid":false,"given":"Ashley J.","family":"Mulford","sequence":"additional","affiliation":[{"name":"Genomic Health Initiative, Endeavor Health, Evanston, IL 60201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan R.","family":"Sanders","sequence":"additional","affiliation":[{"name":"Genomic Health Initiative, Endeavor Health, Evanston, IL 60201, USA"},{"name":"Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Pham","sequence":"additional","affiliation":[{"name":"Department of Neurology, Endeavor Health, Evanston, IL 60201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3017-4584","authenticated-orcid":false,"given":"Alexander","family":"Epshteyn","sequence":"additional","affiliation":[{"name":"Department of Information Technology, Endeavor Health, Skokie, IL 60077, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Demetrius","family":"Maraganore","sequence":"additional","affiliation":[{"name":"Department of Neurology, Endeavor Health, Evanston, IL 60201, USA"},{"name":"Department of Neurology, Tulane University, New Orleans, LA 70118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3973-5437","authenticated-orcid":false,"given":"Katerina","family":"Markopoulou","sequence":"additional","affiliation":[{"name":"Department of Neurology, Endeavor Health, Evanston, IL 60201, USA"},{"name":"University of Chicago Pritzker School of Medicine, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,16]]},"reference":[{"key":"ref_1","unstructured":"(2018). 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