{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:02:06Z","timestamp":1785402126182,"version":"3.56.0"},"reference-count":49,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Australian National Health and Medical Research Council","award":["NHMRC-APP1122387"],"award-info":[{"award-number":["NHMRC-APP1122387"]}]},{"name":"Migraine Research Foundation grant","award":["(2016)"],"award-info":[{"award-number":["(2016)"]}]},{"award":["(2016)"],"award-info":[{"award-number":["(2016)"]}],"id":[{"id":"https:\/\/ror.org\/045e0dn59","id-type":"ROR","asserted-by":"publisher"}]},{"name":"infrastructure purchased with Australian Government EIF Super Science Funds as part of the Therapeutic Innovation Australia\u2014Queensland Node project","award":["(L.R.G.)"],"award-info":[{"award-number":["(L.R.G.)"]}]},{"award":["(L.R.G.)"],"award-info":[{"award-number":["(L.R.G.)"]}],"id":[{"id":"https:\/\/ror.org\/0314h5y94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"PhD scholarship provided by Queensland University of Technology","award":["2021-2024"],"award-info":[{"award-number":["2021-2024"]}]},{"award":["2021-2024"],"award-info":[{"award-number":["2021-2024"]}],"id":[{"id":"https:\/\/ror.org\/00rqy9422","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Migraine is a complex neurovascular disorder with a substantial genetic component, yet many contributing loci remain poorly characterised. Methods: This study investigated the association between 21 biologically prioritised single nucleotide variants (SNVs) and migraine susceptibility in a case-control cohort of 548 individuals of European ancestry, of whom 304 (164 cases, 140 controls) remained after quality control and principal component analysis (PCA). Genotyping was performed using a targeted Sequenom MassARRAY platform, and substantial missingness (mean 30.3% per SNV) was addressed using multiple imputation by chained equations (MICE). Association testing was conducted using three complementary logistic regression frameworks: unadjusted single-variant analysis, covariate-adjusted marginal models, and a multivariable joint model incorporating all SNVs with L2 regularisation. Results: Across analyses, two variants in ASTN2 (rs1052053 and rs6478241) showed the most robust associations with migraine, surviving Bonferroni correction in the joint model (p = 0.001 and p = 0.002, respectively) and false discovery rate (FDR) correction in marginal models (q = 0.003 for both). A third variant, rs7304841 (12p12), demonstrated a risk-increasing effect that reached FDR significance in marginal analysis (q = 0.035) and remained nominally significant in the joint model. In contrast, rs62624978 in CTC1 showed a strong signal in unadjusted analysis (OR = 0.217, p = 0.0014) and remained nominally significant after adjustment (p = 0.011), although it did not survive multiple-testing correction in imputed models. The joint model demonstrated good discriminatory performance (AUC = 0.822), though this is not intended as a predictive tool. Biologically, implicated loci suggest contributions from both neuronal circuit organisation (ASTN2) and telomere and vascular maintenance pathways (CTC1), supporting a broader neurovascular model of migraine susceptibility. Conclusions: These findings are consistent with shared genetic architecture between migraine and microvascular dysfunction, potentially involving endothelial integrity, neurovascular coupling, and cortical excitability mechanisms.<\/jats:p>","DOI":"10.3390\/genes17050541","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T16:54:07Z","timestamp":1777654447000},"page":"541","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring Vascular Contributions to Migraine: Association Analysis of Small Vessel Disease Genetic Variants"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2917-6251","authenticated-orcid":false,"given":"Zizi","family":"Molaee","sequence":"first","affiliation":[{"name":"Genomics Research Centre, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, 60 Musk Ave, Kelvin Grove, QLD 4059, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Al-Fayyadh","sequence":"additional","affiliation":[{"name":"Genomics Research Centre, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, 60 Musk Ave, Kelvin Grove, QLD 4059, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Smith","sequence":"additional","affiliation":[{"name":"Genomics Research Centre, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, 60 Musk Ave, Kelvin Grove, QLD 4059, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4891-4333","authenticated-orcid":false,"given":"Neven","family":"Maksemous","sequence":"additional","affiliation":[{"name":"Genomics Research Centre, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, 60 Musk Ave, Kelvin Grove, QLD 4059, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6774-5475","authenticated-orcid":false,"given":"Lyn R.","family":"Griffiths","sequence":"additional","affiliation":[{"name":"Genomics Research Centre, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, 60 Musk Ave, Kelvin Grove, QLD 4059, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1016\/S0140-6736(18)32279-7","article-title":"Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990\u20132017: A systematic analysis for the Global Burden of Disease Study 2017","volume":"392","author":"James","year":"2018","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1016\/S1474-4422(18)30322-3","article-title":"Global, regional, and national burden of migraine and tension-type headache, 1990\u20132016: A systematic analysis for the Global Burden of Disease Study 2016","volume":"17","author":"Stovner","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1152\/physrev.00034.2015","article-title":"Pathophysiology of migraine: A disorder of sensory processing","volume":"97","author":"Goadsby","year":"2017","journal-title":"Physiol. 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