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Here, we performed a genome-wide association study of 102,084 migraine cases and 771,257 controls and identified 123 loci, of which 86 are previously unknown. These loci provide an opportunity to evaluate shared and distinct genetic components in the two main migraine subtypes: migraine with aura and migraine without aura. Stratification of the risk loci using 29,679 cases with subtype information indicated three risk variants that seem specific for migraine with aura (in\n                    <jats:italic>HMOX2<\/jats:italic>\n                    ,\n                    <jats:italic>CACNA1A<\/jats:italic>\n                    and\n                    <jats:italic>MPPED2<\/jats:italic>\n                    ), two that seem specific for migraine without aura (near\n                    <jats:italic>SPINK2<\/jats:italic>\n                    and near\n                    <jats:italic>FECH<\/jats:italic>\n                    ) and nine that increase susceptibility for migraine regardless of subtype. The new risk loci include genes encoding recent migraine-specific drug targets, namely calcitonin gene-related peptide (\n                    <jats:italic>CALCA\/CALCB<\/jats:italic>\n                    ) and serotonin 1F receptor (\n                    <jats:italic>HTR1F<\/jats:italic>\n                    ). Overall, genomic annotations among migraine-associated variants were enriched in both vascular and central nervous system tissue\/cell types, supporting unequivocally that neurovascular mechanisms underlie migraine pathophysiology.\n                  <\/jats:p>","DOI":"10.1038\/s41588-021-00990-0","type":"journal-article","created":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T12:06:01Z","timestamp":1643889961000},"page":"152-160","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":373,"title":["Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles"],"prefix":"10.1038","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5585-6856","authenticated-orcid":false,"given":"Heidi","family":"Hautakangas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4171-8919","authenticated-orcid":false,"given":"Bendik S.","family":"Winsvold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1631-4069","authenticated-orcid":false,"given":"Sanni E.","family":"Ruotsalainen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyda","family":"Bjornsdottir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5477-7232","authenticated-orcid":false,"given":"Aster V. 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P.G. is a current employee and stockholder of GlaxoSmithKline but work was conducted while employed by Massachusetts General Hospital, Boston, MA, USA. T.F. reports possible competing interest for Electrocore (participation in clinical studies), Novartis (speakers\u2019 honoraria, participation in advisory boards, participation in clinical studies), Teva (speakers\u2019 honoraria, participation in advisory boards), Lilly (speakers\u2019 honoraria, participation in clinical studies), and Bayer (speakers\u2019 honoraria). M. Kallela has served on Advisory Boards for MSD and Allergan; has received funding for travel and\/or speaker honoraria from MSD, Allergan, Teva, Novartis and Genzyme; has received compensation for producing educational material from Teva and Allergan; has received research support from Helsinki University Central Hospital; and holds stock\/stock options and\/or has received Board of Directors compensation from Helsinki Headache Center. T.K. reports having received honoraria from Eli Lilly, Newsenselab and Total for providing methodological advice and from the BMJ for editorial services. A.P. is the Scientific Director of the public\u2013private partnership project FinnGen that has 12 industry partners that provide funding for the FinnGen project. V.A. has served on advisory board for Allergan, Lundbeck, Teva and Lilly. G.M.T. reports consultancy support from Novartis, Allergan, Lilly and Teva, and independent support from Dutch Organization for Scientific Research, the Dutch Heart & Brain Foundations, IRRF and Dioraphte. Other authors report no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}