ABO blood group distribution in migraine patients; the relationship of phenotypes with migraine subtypes, clinical features, and white matter lesions: A Retrospective Case-Control Study

ABO blood group distribution in migraine patients; the relationship of phenotypes with migraine subtypes, clinical features, and white matter lesions: A Retrospective Case-Control Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article ABO blood group distribution in migraine patients; the relationship of phenotypes with migraine subtypes, clinical features, and white matter lesions: A Retrospective Case-Control Study Ferhat KILICASLAN, Erman ALTUNISIK, Yasemin EKMEKYAPAR FIRAT, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8489964/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 02 Apr, 2026 Read the published version in BMC Neurology → Version 1 posted 10 You are reading this latest preprint version Abstract Background Migraine is a common and disabling neurological disorder with a complex and multifactorial pathophysiology. While genetic and vascular mechanisms have been extensively studied, the potential role of the ABO blood group system in migraine susceptibility and clinical characteristics remains unclear. This study aimed to evaluate the distribution of ABO and Rh blood groups in patients with migraine and to investigate their associations with migraine subtypes, clinical features, and white matter lesions (WMLs). Methods This retrospective case–control study included 411 migraine patients aged 18–50 years and 4319 control individuals from the same geographical region. Migraine diagnosis and classification were established according to the International Classification of Headache Disorders, 3rd edition. ABO and Rh blood groups were determined using the gel centrifugation method. Migraine subtypes, clinical characteristics, and the presence of WMLs on cranial magnetic resonance imaging were recorded. Group comparisons and univariate logistic regression analyses were performed. Results Blood group B was significantly less frequent in migraine patients compared with controls (13.4% vs. 18.6%, p = 0.009). In univariate logistic regression analysis, blood group B was associated with lower odds of migraine (OR = 0.67, 95% CI: 0.503–0.906). No significant differences were observed between migraine patients and controls with respect to A, O, and AB blood groups or Rh status. ABO and Rh blood group distributions were not significantly associated with migraine subtypes, the presence of WMLs, headache duration, or monthly headache frequency. Conclusions Blood group B was underrepresented among migraine patients compared with the healthy population from the same geographical region. No associations were identified between ABO or Rh blood groups and migraine subtypes, clinical headache characteristics, or white matter lesions. These findings should be considered hypothesis-generating and require confirmation in larger, multicenter studies. Migraine ABO blood group white matter lesions magnetic resonance imaging Rh factor BACKGROUND Migraine is a common and complex neurological disorder characterized by recurrent headache attacks and a substantial disease burden. Its global prevalence is approximately 12%, and it ranks as the second leading cause of neurological disability worldwide, surpassed only by stroke ( 1 – 3 ). Migraine consists of overlapping phases, including the premonitory, aura, headache, and postdrome phases, all of which contribute to functional impairment and reduced quality of life ( 2 ). Although migraine was long considered a benign condition without lasting consequences, accumulating evidence suggests an association with structural brain changes ( 4 ). In particular, white matter lesions (WMLs), which reflect microvascular injury and are thought to arise from gliosis, demyelination, and axonal loss, have been reported more frequently in individuals with migraine. These lesions have been linked to adverse cognitive and physical outcomes, especially in later life, and migraine has been proposed as a potential risk factor for their development ( 5 ). The ABO blood group system, the first human blood group system to be identified, was discovered in the early 1900s ( 6 ). The ABO gene is located on chromosome 9q34.2 and encodes glycosyltransferases responsible for the synthesis of A and B antigens through modification of the H antigen ( 7 ). Beyond its role in transfusion medicine, the ABO blood group system has been associated with susceptibility to various diseases, particularly infectious, autoimmune, cardiovascular, and inflammatory conditions ( 8 ). Notably, ABO blood groups have been linked to thrombotic and vascular diseases, partly through their influence on circulating levels of coagulation factor VIII and von Willebrand factor ( 9 ). In addition, genetic variants within the ABO locus, such as rs505922, have been associated with cardioembolic and large-vessel ischemic stroke, but not with small-vessel disease, suggesting a selective role in macrovascular pathology ( 10 ). Despite these vascular and genetic links, the relationship between the ABO blood group system and migraine remains poorly defined, and data regarding its association with migraine subtypes, clinical characteristics, and WMLs are limited. Therefore, in this study, we analyzed the distribution of ABO and Rh blood groups in a cohort of 411 patients with migraine and compared these distributions with those of healthy individuals from the same geographical region. We further investigated the associations between blood group distribution and migraine subtypes, clinical features, and the presence of WMLs. METHODS Study design and participants This retrospective case–control study included 411 patients aged 18–50 years who were diagnosed with migraine and admitted to Patnos State Hospital in 2024. The control group consisted of 4319 individuals from the same geographical region whose ABO and Rh blood groups had been determined during routine clinical evaluations. Individuals in the control group had no documented diagnosis of migraine. Migraine diagnosis and classification were established according to the International Classification of Headache Disorders, 3rd edition (ICHD-3). Blood group determination ABO and Rh blood groups were determined using the gel centrifugation method (Odak Diagnostics, Turkey), in accordance with the manufacturer’s instructions. Venous blood samples were collected in EDTA-containing tubes, and blood group analyses were performed in the hospital laboratory under standardized conditions. The study protocol was approved by the Department of Support Services, Provincial Health Directorate, Governorship of Ağrı, Türkiye (Approval No: E-85724094-929-246168351; date: 11 June 2024). Due to the retrospective nature of the study, the requirement for informed consent was waived. Statistical analysis Statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS), version 22.0 (IBM Corp., Armonk, NY, USA). The distribution of continuous variables was assessed using skewness and kurtosis values. Continuous variables were expressed as mean ± standard deviation (SD), and categorical variables were presented as frequencies and percentages [n (%)]. Comparisons between two independent groups were performed using the independent samples t-test for continuous variables and the chi-square test for categorical variables. Comparisons among more than two groups were conducted using one-way analysis of variance (ANOVA), as appropriate. Univariate logistic regression analysis was used to evaluate the association between ABO blood groups and the presence of migraine. A p-value < 0.05 was considered statistically significant. RESULTS A total of 4730 individuals were included in the study, comprising 411 migraine patients and 4319 control subjects. The demographic and clinical characteristics of the migraine patients are summarized in Table 1 . The mean age of the patients was 30.45 ± 8.2 years, and 92.9% were women. The mean duration of migraine attacks was 34.04 ± 30.5 hours, and patients experienced an average of 14.13 ± 7.6 headache days per month. Migraine with aura was present in 6.1% of patients, and white matter lesions (WMLs) were detected on cranial magnetic resonance imaging in 14.1% of the migraine cohort. Table 1 Demographic characteristics of patients with migraine Characteristics (n:411) Patient group (n:411) Mean age (years) 30.45 ± 8.2 Women (%) 92.9 Attack duration (hours) 34.04 ± 30.5 Headache days per month (days) 14.13 ± 7.6 Migraine with aura (%) 6.1 Patients with white matter lesions (%) 14.1 The distribution of ABO blood groups and Rh factor according to migraine characteristics is presented in Table 2 . No statistically significant differences were observed in ABO blood group distribution between patients with and without aura (p > 0.05). Similarly, Rh factor distribution did not differ according to aura status (p > 0.05). The presence of WMLs was also not associated with ABO blood group distribution, with comparable proportions of A, B, O, and AB blood groups among patients with and without WMLs (p > 0.05). In addition, Rh positivity and negativity did not differ significantly according to WML status (p > 0.05). Table 2 Distribution of ABO blood groups and Rh factor according to clinical characteristics in patients Characteristics (n:411) Blood groups n (%) Rh groups n (%) A B O AB p Rh+ Rh- p Without aura 180 (46.6) 49 (12.7) 131 (33.9) 26 (6.7) 0.278 334 (86.5) 52 (13.5) 0.988 With aura 9 (36.0) 6 (24.0) 8 (32.0) 2 (8.0) 22 (88.0) 3 (12.0) WML + 24 (42.9) 12 (21.4) 17 (30.4) 3 (5.4) 0.250 48 (82.8) 10 (17.2) 0.299 WML – 165 (46.5) 43 (12.1) 122 (34.4) 25 (7.0) 308 (87.3) 45 (12.7) p: Pearson Chi-Square Test Abbreviations: WML, white matter lesion. The association between ABO blood groups (A, B, O, and AB) and study groups (migraine patients vs. controls) was initially evaluated using a 4 × 2 Pearson chi-square test. A statistically significant difference in overall ABO blood group distribution was observed between the patient and control groups (χ² = 8.23, df = 3, p = 0.041); however, the effect size was small (Cramer’s V = 0.042). To identify the blood group primarily contributing to this difference, an explanatory post-hoc 2 × 2 chi-square analysis was performed. This analysis demonstrated that blood group B was significantly less frequent in the migraine group than in the control group (13.4% vs. 18.6%; χ² = 6.92, p = 0.009), whereas no significant differences were observed for the other blood groups. Based on this finding, subsequent analyses focused on comparisons between blood group B and non-B blood groups (A, O, and AB) (Table 3 ). Table 3 Comparison of blood group B and Rh factor frequency between patient and control groups Characteristics (n:4730) Patient (n:411) Control (n:4319) p ABO groups 0 141 (34.3) 1370 (31.7) 0.041* A 187 (45.4) 1826 (42.3) B 55 (13.4) 804 (18.6) AB 28 (6.8) 319 (7.4) B Group and others 0, A, AB 356 (86.6) 3515 (81.4) 0.009* B 55 (13.4) 804 (18.6) Rh Groups Rh- 55 (13.4) 555 (12.9) 0.759 Rh+ 356 (86.6) 3764 (87.1) p: Pearson Chi-Square Test In univariate logistic regression analysis, blood group B was associated with a significantly lower likelihood of migraine (OR = 0.67, 95% CI 0.503–0.906; p = 0.009) (Table 4 ). Subgroup analyses stratified by Rh factor were conducted; however, no consistent or statistically robust associations were identified. Table 4 Univariate logistic regression analysis for the association between blood group B and migraine status Variable OR 95% CI p value Blood group B (vs non-B) 0.67 0.503–0.906 0.009 Univariate logistic regression analysis was performed. The dependent variable was migraine status (patient vs control). Blood group B was compared with non-B blood groups (O, A, and AB). OR, odds ratio; CI, confidence interval. DISCUSSION In this study, the association between ABO blood group distribution and migraine status was comprehensively evaluated. Although a statistically significant difference in overall ABO blood group distribution was observed between migraine patients and control subjects, the small effect size suggests that the clinical relevance of this association is limited. Explanatory post-hoc analyses indicated that this overall difference was primarily driven by the lower frequency of blood group B among patients with migraine. Previous studies have investigated the relationship between ABO blood groups and various neuropsychiatric disorders. In patients with multiple sclerosis, blood group AB has been reported as a potential risk factor, whereas blood group O may have a protective role ( 11 ). Another study demonstrated that psychiatric disorders occurred nearly three times more frequently in individuals with blood group AB compared with non-AB individuals ( 12 ). In addition, a population-based study conducted in the United States reported higher mean depression scores among individuals with blood group O ( 13 ). These findings suggest that blood group antigens may influence susceptibility to neuropsychiatric conditions. The relationship between psychiatric disorders and blood groups has been interpreted in the context of neurotransmitter and enzyme metabolism, with genetic susceptibility potentially mediated through enzymatic and molecular pathways ( 12 ). Neurogenic inflammation, involving mediators such as histamine and calcitonin gene-related protein (CGRP), is widely accepted as a central mechanism in migraine pathophysiology ( 14 ). Therefore, it is conceivable that the neurotransmitter- and enzyme-related mechanisms proposed for the association between ABO blood groups and psychiatric disorders may also be relevant to migraine. Differences in neuroimmune or neuroinflammatory mediator profiles across ABO blood groups could theoretically influence migraine susceptibility. The inverse association observed between blood group B and migraine status may point to potential roles of ABO antigens in vascular, inflammatory, or neuroimmune pathways. However, because this association was identified through univariate analyses and accounted for only a small proportion of variance, it would be inappropriate to interpret the finding as evidence of a protective effect. Rather, the results suggest that ABO blood groups may play a secondary or indirect role in migraine pathophysiology. Subgroup analyses stratified by Rh factor did not demonstrate a consistent or robust pattern of association, and no evidence was found to support a modifying effect of Rh factor on the relationship between ABO blood groups and migraine status. These Rh-stratified analyses were exploratory in nature and should be interpreted with caution. The established association between ABO blood group distributions and thrombotic vascular diseases has prompted extensive investigation in cerebrovascular disorders. In one study, blood group AB was found to be significantly more frequent among patients with ischemic stroke ( 15 ). Similarly, a study conducted in the United States reported that individuals with blood group AB had an approximately twofold increased risk of ischemic stroke ( 9 ). Another study demonstrated that non-O blood group phenotypes were associated with a higher risk of stroke compared with the O phenotype ( 16 ). These findings support the notion that ABO blood groups may influence vascular disease risk, although their relevance to migraine—particularly in the absence of overt cerebrovascular pathology—remains uncertain. The impact of ABO blood groups on neuroimmune or neuroinflammatory processes in migraine is not well defined. To date, no definitive pathophysiological association between ABO blood groups and migraine has been established, and the available evidence remains limited and inconsistent. Importantly, there is no existing evidence to support the hypothesis that blood group B confers protection against migraine. In the present study, although a statistically significant difference in overall ABO blood group distribution was observed between patients and controls, the small effect size indicates that the clinical implications of this finding are modest. The observed difference was primarily attributable to the lower frequency of blood group B among migraine patients. Limitations Several limitations of this study should be acknowledged. First, the retrospective design limits causal inference. Second, the analyses were primarily univariate, and residual confounding cannot be excluded. Third, although genetic susceptibility is discussed, direct genetic analyses of the ABO locus were not performed, and the findings therefore cannot be directly linked to specific genetic variants. Finally, the study population was derived from a single geographical region, which may limit the generalizability of the results. Conclusions In this study, we investigated the relationship between ABO blood group distribution and migraine, including migraine subtypes, clinical characteristics, and white matter lesions, within a single geographical region. We observed that blood group B was less frequent among migraine patients than among healthy individuals from the same population. While this finding suggests a possible association, its clinical relevance appears limited, and it should be interpreted as hypothesis-generating. Further studies incorporating multivariable models, genetic analyses, and prospective designs are required to clarify the functional role of ABO blood groups in migraine susceptibility and pathophysiology. Declarations Ethics approval and consent to participate This study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki. The study protocol was approved by the Department of Support Services, Provincial Health Directorate, Governorship of Ağrı, Türkiye (Approval No: E-85724094-929-246168351; date: 11 June 2024). Due to the retrospective nature of the study, the requirement for informed consent was waived. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Author Contribution Conception and design of the work was done by FK. Data collection was handled by FK, EA and YEF. Data analysis was done by KOL. All the authors were responsible of the interpretation of data, drafting the manuscript, revising and final approval of the version to be published. Acknowledgement We thank Sırma Geyik for her insightful and helpful comments on the manuscript. Data Availability The datasets generated and/or analyzed during the current study are not publicly available due to institutional data protection policies but are available from the corresponding author on reasonable request. References Pescador Ruschel MA, De Jesus O. Migraine headache. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024. Available from: NCBI Bookshelf. Accessed 15 Oct 2025. Aguilar-Shea AL, Díaz-de-Terán J. 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ABO blood group system and the coronary artery disease: an updated systematic review and meta-analysis. Sci Rep. 2016;6:23250. Zakai NA, Judd SE, Alexander K, McClure LA, Kissela BM, Howard G, et al. ABO blood type and stroke risk: the Reasons for Geographic and Racial Differences in Stroke Study. J Thromb Haemost. 2014;12(4):564–70. Williams FMK, Carter AM, Hysi PG, Surdulescu G, Hodgkiss D, Soranzo N, et al. Ischemic stroke is associated with the ABO locus: the EuroCLOT study. Ann Neurol. 2013;73(1):16–31. Lopetegi I, Muñoz-Lopetegi A, Arruti M, Prada A, Urcelay S, Olascoaga J, et al. ABO blood group distributions in multiple sclerosis patients from the Basque Country: O – as a protective factor. Mult Scler J Exp Transl Clin. 2019;5(4):2055217319888954. Pisk SV, Vuk T, Ivezić E, Jukić I, Bingulac-Popović J, Filipčić I. ABO blood groups and psychiatric disorders: a Croatian study. Blood Transfus. 2019;17(1):66–71. Singg S, Lewis JL. Depression and blood types. Psychol Rep. 2001;88(3):725–6. Yuan H, Silberstein SD. Histamine and migraine. Headache. 2018;58(1):184–93. Lotz RC, Welter C da, Ramos S, Ferreira SA, Cabral LE, de França NL. ABO blood group system and occurrence of ischemic stroke. Arq Neuropsiquiatr. 2021;79(12):1070–5. Dentali F, Sironi AP, Ageno W, Crestani S, Franchini M. ABO blood groups and vascular disease: a systematic review and meta-analysis. J Thromb Haemost. 2012;10(7):1319–28. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 02 Apr, 2026 Read the published version in BMC Neurology → Version 1 posted Editorial decision: Revision requested 10 Mar, 2026 Reviews received at journal 09 Mar, 2026 Reviewers agreed at journal 03 Mar, 2026 Reviews received at journal 25 Feb, 2026 Reviewers agreed at journal 18 Feb, 2026 Reviewers invited by journal 15 Jan, 2026 Editor invited by journal 07 Jan, 2026 Editor assigned by journal 06 Jan, 2026 Submission checks completed at journal 06 Jan, 2026 First submitted to journal 31 Dec, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8489964","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":575232348,"identity":"9b55b211-98d7-47e0-b947-b18e94f44258","order_by":0,"name":"Ferhat KILICASLAN","email":"","orcid":"","institution":"Patnos State Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ferhat","middleName":"","lastName":"KILICASLAN","suffix":""},{"id":575232349,"identity":"edcf3ec3-2599-4b34-a662-c1c8207234a0","order_by":1,"name":"Erman ALTUNISIK","email":"","orcid":"","institution":"Gaziantep State 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16:13:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":585929,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8489964/v1/8c8d3d7d-0764-4e63-83c3-c14cceed321b.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"ABO blood group distribution in migraine patients; the relationship of phenotypes with migraine subtypes, clinical features, and white matter lesions: A Retrospective Case-Control Study","fulltext":[{"header":"BACKGROUND","content":"\u003cp\u003eMigraine is a common and complex neurological disorder characterized by recurrent headache attacks and a substantial disease burden. Its global prevalence is approximately 12%, and it ranks as the second leading cause of neurological disability worldwide, surpassed only by stroke (\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Migraine consists of overlapping phases, including the premonitory, aura, headache, and postdrome phases, all of which contribute to functional impairment and reduced quality of life (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAlthough migraine was long considered a benign condition without lasting consequences, accumulating evidence suggests an association with structural brain changes (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). In particular, white matter lesions (WMLs), which reflect microvascular injury and are thought to arise from gliosis, demyelination, and axonal loss, have been reported more frequently in individuals with migraine. These lesions have been linked to adverse cognitive and physical outcomes, especially in later life, and migraine has been proposed as a potential risk factor for their development (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe ABO blood group system, the first human blood group system to be identified, was discovered in the early 1900s (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). The ABO gene is located on chromosome 9q34.2 and encodes glycosyltransferases responsible for the synthesis of A and B antigens through modification of the H antigen (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Beyond its role in transfusion medicine, the ABO blood group system has been associated with susceptibility to various diseases, particularly infectious, autoimmune, cardiovascular, and inflammatory conditions (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eNotably, ABO blood groups have been linked to thrombotic and vascular diseases, partly through their influence on circulating levels of coagulation factor VIII and von Willebrand factor (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). In addition, genetic variants within the ABO locus, such as rs505922, have been associated with cardioembolic and large-vessel ischemic stroke, but not with small-vessel disease, suggesting a selective role in macrovascular pathology (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDespite these vascular and genetic links, the relationship between the ABO blood group system and migraine remains poorly defined, and data regarding its association with migraine subtypes, clinical characteristics, and WMLs are limited. Therefore, in this study, we analyzed the distribution of ABO and Rh blood groups in a cohort of 411 patients with migraine and compared these distributions with those of healthy individuals from the same geographical region. We further investigated the associations between blood group distribution and migraine subtypes, clinical features, and the presence of WMLs.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and participants\u003c/h2\u003e \u003cp\u003eThis retrospective case\u0026ndash;control study included 411 patients aged 18\u0026ndash;50 years who were diagnosed with migraine and admitted to Patnos State Hospital in 2024. The control group consisted of 4319 individuals from the same geographical region whose ABO and Rh blood groups had been determined during routine clinical evaluations. Individuals in the control group had no documented diagnosis of migraine.\u003c/p\u003e \u003cp\u003eMigraine diagnosis and classification were established according to the International Classification of Headache Disorders, 3rd edition (ICHD-3).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eBlood group determination\u003c/h3\u003e\n\u003cp\u003eABO and Rh blood groups were determined using the gel centrifugation method (Odak Diagnostics, Turkey), in accordance with the manufacturer\u0026rsquo;s instructions. Venous blood samples were collected in EDTA-containing tubes, and blood group analyses were performed in the hospital laboratory under standardized conditions. The study protocol was approved by the Department of Support Services, Provincial Health Directorate, Governorship of Ağrı, T\u0026uuml;rkiye (Approval No: E-85724094-929-246168351; date: 11 June 2024). Due to the retrospective nature of the study, the requirement for informed consent was waived.\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analyses were performed using the Statistical Package for the Social Sciences (SPSS), version 22.0 (IBM Corp., Armonk, NY, USA). The distribution of continuous variables was assessed using skewness and kurtosis values. Continuous variables were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD), and categorical variables were presented as frequencies and percentages [n (%)].\u003c/p\u003e \u003cp\u003eComparisons between two independent groups were performed using the independent samples t-test for continuous variables and the chi-square test for categorical variables. Comparisons among more than two groups were conducted using one-way analysis of variance (ANOVA), as appropriate. Univariate logistic regression analysis was used to evaluate the association between ABO blood groups and the presence of migraine. A p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eA total of 4730 individuals were included in the study, comprising 411 migraine patients and 4319 control subjects. The demographic and clinical characteristics of the migraine patients are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The mean age of the patients was 30.45\u0026thinsp;\u0026plusmn;\u0026thinsp;8.2 years, and 92.9% were women. The mean duration of migraine attacks was 34.04\u0026thinsp;\u0026plusmn;\u0026thinsp;30.5 hours, and patients experienced an average of 14.13\u0026thinsp;\u0026plusmn;\u0026thinsp;7.6 headache days per month. Migraine with aura was present in 6.1% of patients, and white matter lesions (WMLs) were detected on cranial magnetic resonance imaging in 14.1% of the migraine cohort.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic characteristics of patients with migraine\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics (n:411)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePatient group (n:411)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean age (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30.45\u0026thinsp;\u0026plusmn;\u0026thinsp;8.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWomen (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e92.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAttack duration (hours)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34.04\u0026thinsp;\u0026plusmn;\u0026thinsp;30.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeadache days per month (days)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14.13\u0026thinsp;\u0026plusmn;\u0026thinsp;7.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMigraine with aura (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatients with white matter lesions (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe distribution of ABO blood groups and Rh factor according to migraine characteristics is presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. No statistically significant differences were observed in ABO blood group distribution between patients with and without aura (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Similarly, Rh factor distribution did not differ according to aura status (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). The presence of WMLs was also not associated with ABO blood group distribution, with comparable proportions of A, B, O, and AB blood groups among patients with and without WMLs (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). In addition, Rh positivity and negativity did not differ significantly according to WML status (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDistribution of ABO blood groups and Rh factor according to clinical characteristics in patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003cp\u003e(n:411)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c6\" namest=\"c2\"\u003e \u003cp\u003eBlood groups n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e \u003cp\u003eRh groups n (%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eO\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eRh+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eRh-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eWithout aura\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e180 (46.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49 (12.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e131 (33.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e26 (6.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.278\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e334 (86.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e52 (13.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.988\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eWith aura\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (36.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (24.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (32.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (8.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e22 (88.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3 (12.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eWML +\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (42.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (21.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17 (30.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (5.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.250\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e48 (82.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e10 (17.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.299\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eWML \u0026ndash;\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e165 (46.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43 (12.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e122 (34.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25 (7.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e308 (87.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e45 (12.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003ep: Pearson Chi-Square Test Abbreviations: WML, white matter lesion.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe association between ABO blood groups (A, B, O, and AB) and study groups (migraine patients vs. controls) was initially evaluated using a 4 \u0026times; 2 Pearson chi-square test. A statistically significant difference in overall ABO blood group distribution was observed between the patient and control groups (χ\u0026sup2; = 8.23, df\u0026thinsp;=\u0026thinsp;3, p\u0026thinsp;=\u0026thinsp;0.041); however, the effect size was small (Cramer\u0026rsquo;s V\u0026thinsp;=\u0026thinsp;0.042). To identify the blood group primarily contributing to this difference, an explanatory post-hoc 2 \u0026times; 2 chi-square analysis was performed. This analysis demonstrated that blood group B was significantly less frequent in the migraine group than in the control group (13.4% vs. 18.6%; χ\u0026sup2; = 6.92, p\u0026thinsp;=\u0026thinsp;0.009), whereas no significant differences were observed for the other blood groups. Based on this finding, subsequent analyses focused on comparisons between blood group B and non-B blood groups (A, O, and AB) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of blood group B and Rh factor frequency between patient and control groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eCharacteristics (n:4730)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePatient (n:411)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eControl (n:4319)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e\u003cb\u003eABO groups\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e141 (34.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1370 (31.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e\u003cb\u003e0.041*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eA\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e187 (45.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1826 (42.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eB\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e55 (13.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e804 (18.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAB\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e28 (6.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e319 (7.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eB Group and others\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e0, A, AB\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e356 (86.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3515 (81.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003e0.009*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eB\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e55 (13.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e804 (18.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eRh Groups\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eRh-\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e55 (13.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e555 (12.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.759\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eRh+\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e356 (86.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3764 (87.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003ep: Pearson Chi-Square Test\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn univariate logistic regression analysis, blood group B was associated with a significantly lower likelihood of migraine (OR\u0026thinsp;=\u0026thinsp;0.67, 95% CI 0.503\u0026ndash;0.906; p\u0026thinsp;=\u0026thinsp;0.009) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Subgroup analyses stratified by Rh factor were conducted; however, no consistent or statistically robust associations were identified.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnivariate logistic regression analysis for the association between blood group B and migraine status\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e95% CI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003eBlood group B (vs non-B)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e0.503\u0026ndash;0.906\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.009\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eUnivariate logistic regression analysis was performed. The dependent variable was migraine status (patient vs control). Blood group B was compared with non-B blood groups (O, A, and AB). OR, odds ratio; CI, confidence interval.\u003c/em\u003e\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eIn this study, the association between ABO blood group distribution and migraine status was comprehensively evaluated. Although a statistically significant difference in overall ABO blood group distribution was observed between migraine patients and control subjects, the small effect size suggests that the clinical relevance of this association is limited. Explanatory post-hoc analyses indicated that this overall difference was primarily driven by the lower frequency of blood group B among patients with migraine. Previous studies have investigated the relationship between ABO blood groups and various neuropsychiatric disorders. In patients with multiple sclerosis, blood group AB has been reported as a potential risk factor, whereas blood group O may have a protective role (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Another study demonstrated that psychiatric disorders occurred nearly three times more frequently in individuals with blood group AB compared with non-AB individuals (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). In addition, a population-based study conducted in the United States reported higher mean depression scores among individuals with blood group O (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). These findings suggest that blood group antigens may influence susceptibility to neuropsychiatric conditions.\u003c/p\u003e \u003cp\u003eThe relationship between psychiatric disorders and blood groups has been interpreted in the context of neurotransmitter and enzyme metabolism, with genetic susceptibility potentially mediated through enzymatic and molecular pathways (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Neurogenic inflammation, involving mediators such as histamine and calcitonin gene-related protein (CGRP), is widely accepted as a central mechanism in migraine pathophysiology (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Therefore, it is conceivable that the neurotransmitter- and enzyme-related mechanisms proposed for the association between ABO blood groups and psychiatric disorders may also be relevant to migraine. Differences in neuroimmune or neuroinflammatory mediator profiles across ABO blood groups could theoretically influence migraine susceptibility.\u003c/p\u003e \u003cp\u003eThe inverse association observed between blood group B and migraine status may point to potential roles of ABO antigens in vascular, inflammatory, or neuroimmune pathways. However, because this association was identified through univariate analyses and accounted for only a small proportion of variance, it would be inappropriate to interpret the finding as evidence of a protective effect. Rather, the results suggest that ABO blood groups may play a secondary or indirect role in migraine pathophysiology. Subgroup analyses stratified by Rh factor did not demonstrate a consistent or robust pattern of association, and no evidence was found to support a modifying effect of Rh factor on the relationship between ABO blood groups and migraine status. These Rh-stratified analyses were exploratory in nature and should be interpreted with caution.\u003c/p\u003e \u003cp\u003eThe established association between ABO blood group distributions and thrombotic vascular diseases has prompted extensive investigation in cerebrovascular disorders. In one study, blood group AB was found to be significantly more frequent among patients with ischemic stroke (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Similarly, a study conducted in the United States reported that individuals with blood group AB had an approximately twofold increased risk of ischemic stroke (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Another study demonstrated that non-O blood group phenotypes were associated with a higher risk of stroke compared with the O phenotype (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). These findings support the notion that ABO blood groups may influence vascular disease risk, although their relevance to migraine\u0026mdash;particularly in the absence of overt cerebrovascular pathology\u0026mdash;remains uncertain.\u003c/p\u003e \u003cp\u003eThe impact of ABO blood groups on neuroimmune or neuroinflammatory processes in migraine is not well defined. To date, no definitive pathophysiological association between ABO blood groups and migraine has been established, and the available evidence remains limited and inconsistent. Importantly, there is no existing evidence to support the hypothesis that blood group B confers protection against migraine. In the present study, although a statistically significant difference in overall ABO blood group distribution was observed between patients and controls, the small effect size indicates that the clinical implications of this finding are modest. The observed difference was primarily attributable to the lower frequency of blood group B among migraine patients.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eSeveral limitations of this study should be acknowledged. First, the retrospective design limits causal inference. Second, the analyses were primarily univariate, and residual confounding cannot be excluded. Third, although genetic susceptibility is discussed, direct genetic analyses of the ABO locus were not performed, and the findings therefore cannot be directly linked to specific genetic variants. Finally, the study population was derived from a single geographical region, which may limit the generalizability of the results.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn this study, we investigated the relationship between ABO blood group distribution and migraine, including migraine subtypes, clinical characteristics, and white matter lesions, within a single geographical region. We observed that blood group B was less frequent among migraine patients than among healthy individuals from the same population. While this finding suggests a possible association, its clinical relevance appears limited, and it should be interpreted as hypothesis-generating. Further studies incorporating multivariable models, genetic analyses, and prospective designs are required to clarify the functional role of ABO blood groups in migraine susceptibility and pathophysiology.\u003c/p\u003e"},{"header":"Declarations","content":" \u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e \u003cp\u003e This study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki. The study protocol was approved by the Department of Support Services, Provincial Health Directorate, Governorship of Ağrı, T\u0026uuml;rkiye (Approval No: E-85724094-929-246168351; date: 11 June 2024). Due to the retrospective nature of the study, the requirement for informed consent was waived.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003eNot applicable.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eConception and design of the work was done by FK. Data collection was handled by FK, EA and YEF. Data analysis was done by KOL. All the authors were responsible of the interpretation of data, drafting the manuscript, revising and final approval of the version to be published.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe thank Sırma Geyik for her insightful and helpful comments on the manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets generated and/or analyzed during the current study are not publicly available due to institutional data protection policies but are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003ePescador Ruschel MA, De Jesus O. Migraine headache. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024. Available from: NCBI Bookshelf. Accessed 15 Oct 2025.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAguilar-Shea AL, D\u0026iacute;az-de-Ter\u0026aacute;n J. Migraine review for general practice. Aten Primaria. 2022;54(2):102170.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchramm S, B\u0026ouml;rner C, Reichert M, Baum T, Zimmer C, Heinen F, et al. Functional magnetic resonance imaging in migraine: a systematic review. Cephalalgia. 2023;43(2):3331024221128278.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBai X, Wang W, Zhang X, Hu Z, Zhang X, Zhang Y, et al. Hyperperfusion of bilateral amygdala in patients with chronic migraine: an arterial spin-labeled magnetic resonance imaging study. J Headache Pain. 2023;24(1):1\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBashir A, Lipton RB, Ashina S, Ashina M. Migraine and structural changes in the brain: a systematic review and meta-analysis. Neurology. 2013;81(14):1260\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLesky E. Viennese serological research about the year 1900: its contribution to the development of clinical medicine. Bull N Y Acad Med. 1973;49(2):100\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYamamoto F, McNeill PD, Hakomori SI. Genomic organization of human histo-blood group ABO genes. Glycobiology. 1995;5(1):51\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen Z, Yang SH, Xu H, Li JJ. ABO blood group system and the coronary artery disease: an updated systematic review and meta-analysis. Sci Rep. 2016;6:23250.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZakai NA, Judd SE, Alexander K, McClure LA, Kissela BM, Howard G, et al. ABO blood type and stroke risk: the Reasons for Geographic and Racial Differences in Stroke Study. J Thromb Haemost. 2014;12(4):564\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWilliams FMK, Carter AM, Hysi PG, Surdulescu G, Hodgkiss D, Soranzo N, et al. Ischemic stroke is associated with the ABO locus: the EuroCLOT study. Ann Neurol. 2013;73(1):16\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLopetegi I, Mu\u0026ntilde;oz-Lopetegi A, Arruti M, Prada A, Urcelay S, Olascoaga J, et al. ABO blood group distributions in multiple sclerosis patients from the Basque Country: O\u0026thinsp;\u0026ndash;\u0026thinsp;as a protective factor. Mult Scler J Exp Transl Clin. 2019;5(4):2055217319888954.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePisk SV, Vuk T, Ivezić E, Jukić I, Bingulac-Popović J, Filipčić I. ABO blood groups and psychiatric disorders: a Croatian study. Blood Transfus. 2019;17(1):66\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSingg S, Lewis JL. Depression and blood types. Psychol Rep. 2001;88(3):725\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYuan H, Silberstein SD. Histamine and migraine. Headache. 2018;58(1):184\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLotz RC, Welter C da, Ramos S, Ferreira SA, Cabral LE, de Fran\u0026ccedil;a NL. ABO blood group system and occurrence of ischemic stroke. Arq Neuropsiquiatr. 2021;79(12):1070\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDentali F, Sironi AP, Ageno W, Crestani S, Franchini M. ABO blood groups and vascular disease: a systematic review and meta-analysis. J Thromb Haemost. 2012;10(7):1319\u0026ndash;28.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Migraine, ABO blood group, white matter lesions, magnetic resonance imaging, Rh factor","lastPublishedDoi":"10.21203/rs.3.rs-8489964/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8489964/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e \u003cp\u003eMigraine is a common and disabling neurological disorder with a complex and multifactorial pathophysiology. While genetic and vascular mechanisms have been extensively studied, the potential role of the ABO blood group system in migraine susceptibility and clinical characteristics remains unclear. This study aimed to evaluate the distribution of ABO and Rh blood groups in patients with migraine and to investigate their associations with migraine subtypes, clinical features, and white matter lesions (WMLs).\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThis retrospective case\u0026ndash;control study included 411 migraine patients aged 18\u0026ndash;50 years and 4319 control individuals from the same geographical region. Migraine diagnosis and classification were established according to the International Classification of Headache Disorders, 3rd edition. ABO and Rh blood groups were determined using the gel centrifugation method. Migraine subtypes, clinical characteristics, and the presence of WMLs on cranial magnetic resonance imaging were recorded. Group comparisons and univariate logistic regression analyses were performed.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eBlood group B was significantly less frequent in migraine patients compared with controls (13.4% vs. 18.6%, p\u0026thinsp;=\u0026thinsp;0.009). In univariate logistic regression analysis, blood group B was associated with lower odds of migraine (OR\u0026thinsp;=\u0026thinsp;0.67, 95% CI: 0.503\u0026ndash;0.906). No significant differences were observed between migraine patients and controls with respect to A, O, and AB blood groups or Rh status. ABO and Rh blood group distributions were not significantly associated with migraine subtypes, the presence of WMLs, headache duration, or monthly headache frequency.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions\u003c/b\u003e\u003c/p\u003e \u003cp\u003eBlood group B was underrepresented among migraine patients compared with the healthy population from the same geographical region. No associations were identified between ABO or Rh blood groups and migraine subtypes, clinical headache characteristics, or white matter lesions. These findings should be considered hypothesis-generating and require confirmation in larger, multicenter studies.\u003c/p\u003e","manuscriptTitle":"ABO blood group distribution in migraine patients; the relationship of phenotypes with migraine subtypes, clinical features, and white matter lesions: A Retrospective Case-Control Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-20 11:41:18","doi":"10.21203/rs.3.rs-8489964/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-03-10T10:20:51+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-09T12:30:18+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"324896830386294176080231538293671120337","date":"2026-03-03T07:20:26+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-25T19:04:25+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"47534995508968294464248422706350253983","date":"2026-02-18T15:02:29+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-15T19:04:27+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-01-07T10:16:12+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-06T05:18:56+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-06T05:17:18+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Neurology","date":"2025-12-31T12:48:59+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"54255c29-f5e6-4965-b0d6-cd90392987cb","owner":[],"postedDate":"January 20th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-04-07T16:06:50+00:00","versionOfRecord":{"articleIdentity":"rs-8489964","link":"https://doi.org/10.1186/s12883-026-04872-y","journal":{"identity":"bmc-neurology","isVorOnly":false,"title":"BMC Neurology"},"publishedOn":"2026-04-02 15:58:32","publishedOnDateReadable":"April 2nd, 2026"},"versionCreatedAt":"2026-01-20 11:41:18","video":"","vorDoi":"10.1186/s12883-026-04872-y","vorDoiUrl":"https://doi.org/10.1186/s12883-026-04872-y","workflowStages":[]},"version":"v1","identity":"rs-8489964","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8489964","identity":"rs-8489964","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}