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Genetic research on migraine in Veterans and its link to psychiatric comorbidities is limited. We present a meta-analysis of a genome-wide association study (GWAS) of migraine in a predominantly male sample of over 433,000 Veterans, including 87,859 cases, from the Million Veteran Program (MVP), identifying 49 genome-wide significant loci, with 36 novel to this study, of which 7 replicated in an independent prior GWAS (after Bonferroni correction for number of loci tested). Our analyses revealed 283 genes, including some newly associated with migraine:\n                    <jats:italic>MAML3, CELF4, IRX1, ASXL1, SPOCD1, CXCL<\/jats:italic>\n                    , and\n                    <jats:italic>TLR4<\/jats:italic>\n                    . In silico analyses showed enrichment in brain and uterine tissues, which may reflect broader hormonal or neuroendocrine pathways. Compared to previous migraine GWAS, our results show minimal vascular tissue enrichment, potentially reflecting the sample composition, which was predominantly men and Veterans. Migraine SNP-based heritability was 10% for men and 16% for women, and several sex-specific loci were identified through sex-stratified analyses. Despite high genetic correlations with neuropsychiatric disorders \u2013 including post-traumatic stress disorder, depression, and traumatic brain injury \u2013 Mendelian randomization analyses found no causal links. Finally, we prioritized potential migraine drug targets, including losmapimod (which reduces production of toxic DUX4 protein) and\n                    <jats:italic>TLR4<\/jats:italic>\n                    antagonists.\n                  <\/jats:p>","DOI":"10.1038\/s41380-025-03392-4","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T07:03:56Z","timestamp":1766127836000},"page":"2660-2674","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A multi-ancestry meta genome-wide association study of migraine among veterans:\u00a0associations with traumatic brain injury, depression, and post-traumatic stress disorder"],"prefix":"10.1038","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4112-5232","authenticated-orcid":false,"given":"Marianna","family":"Gasperi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara Brin","family":"Rosenthal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam X.","family":"Maihofer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armand","family":"Gerstenberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9513-5124","authenticated-orcid":false,"given":"Daniel","family":"Dochtermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9839-8667","authenticated-orcid":false,"given":"H\u00e9l\u00e8ne","family":"Choquet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Pressman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew S.","family":"Panizzon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9564-2871","authenticated-orcid":false,"given":"Murray B.","family":"Stein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathaniel M.","family":"Schuster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9047-3762","authenticated-orcid":false,"given":"Saiju","family":"Pyarajan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"VA Million Veteran Program","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niloofar","family":"Afari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5766-8923","authenticated-orcid":false,"given":"Caroline M.","family":"Nievergelt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,19]]},"reference":[{"key":"3392_CR1","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1111\/head.13709","volume":"60","author":"BR Scott","year":"2020","unstructured":"Scott BR, Uomoto JM, Barry ES. 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Dr. Stein has stock options in Oxeia Biopharmaceuticals and EpiVario. He has been paid for his editorial work on\n                      Depression and\n                      Anxiety (Editor-in-Chief),\n                      Biological\n                      Psychiatry (Deputy Editor), and\n                      UpToDate\n                      (Co-Editor-in-Chief for Psychiatry). He is on the scientific advisory board of the Brain and Behavior Research Foundation and the Anxiety and Depression Association of America. The other authors have no conflicts of interest to report. Dr. Gasperi is supported by the VA 1IK2CX002107 and 1I01RD001420 from the US Department of Veterans Affairs Clinical Science Research and Development Service. Dr. Nievergelt is funded by the Department of Veterans Affairs, Biomedical Laboratory Research and Development (BLRD) BX005920, and Rehabilitation Research and Development (RR&D) RX004293 and by NIMH R01MH106595. This research was partially supported by the Altman Clinical & Translational Research Institute (ACTRI) at the University of California, San Diego. The ACTRI is funded by awards issued by the National Center for Advancing Translational Sciences, NIH UL1TR001442. Genotyping of the GERA cohort was funded by a grant from the National Institute on Aging, National Institute of Mental Health, and National Institute of Health Common Fund (RC2 AG036607). The study of Choquet et al. was funded by a grant from the National Institute for Neurological Disorders and Stroke (NINDS) R01NS080863. Dr. Choquet is supported by the National Eye Institute (NEI) grant R01EY033010, and by the National Cancer Institute (NCI) R01CA241623.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}