{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T05:32:06Z","timestamp":1792647126310,"version":"4.5.0"},"reference-count":78,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T00:00:00Z","timestamp":1665532800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Migraine and headache frequently co-occur with type 2 diabetes (T2D), suggesting a shared aetiology between the two conditions. We used genome-wide association study (GWAS) data to investigate the genetic overlap and causal relationship between migraine and headache with T2D. Using linkage disequilibrium score regression (LDSC), we found a significant genetic correlation between migraine and T2D (rg = 0.06, p = 1.37 \u00d7 10\u22125) and between headache and T2D (rg = 0.07, p = 3.0 \u00d7 10\u22124). Using pairwise GWAS (GWAS-PW) analysis, we identified 11 pleiotropic regions between migraine and T2D and 5 pleiotropic regions between headache and T2D. Cross-trait SNP meta-analysis identified 23 novel SNP loci (Pmeta &lt; 5 \u00d7 10\u22128) associated with migraine and T2D, and three novel SNP loci associated with headache and T2D. Cross-trait gene-based overlap analysis identified 33 genes significantly associated (Pgene-based &lt; 3.85 \u00d7 10\u22126) with migraine and T2D, and 11 genes associated with headache and T2D, with 7 genes (EHMT2, SLC44A4, PLEKHA1, CFDP1, TMEM170A, CHST6, and BCAR1) common between them. There was also a significant overlap of genes nominally associated (Pgene-based &lt; 0.05) with both migraine and T2D (Pbinomial-test = 2.83 \u00d7 10\u221246) and headache and T2D (Pbinomial-test = 4.08 \u00d7 10\u221229). Mendelian randomisation (MR) analyses did not provide consistent evidence for a causal relationship between migraine and T2D. However, we found headache was causally associated (inverse-variance weighted, ORIVW = 0.90, Pivw = 7 \u00d7 10\u22123) with T2D. Our findings robustly confirm the comorbidity of migraine and headache with T2D, with shared genetically controlled biological mechanisms contributing to their co-occurrence, and evidence for a causal relationship between headache and T2D.<\/jats:p>","DOI":"10.3390\/genes13101845","type":"journal-article","created":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T20:53:29Z","timestamp":1665608009000},"page":"1845","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Genetic Overlap Analysis Identifies a Shared Etiology between Migraine and Headache with Type 2 Diabetes"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7370-2535","authenticated-orcid":false,"given":"Md Rafiqul","family":"Islam","sequence":"first","affiliation":[{"name":"Statistical and Genomic Epidemiology Laboratory, School of Biomedical Sciences, Faculty of Health, Centre for Genomics and Personalised Health, Queensland University of Technology, Kelvin Grove, QLD 4000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"The International Headache Genetics Consortium (IHGC)","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7159-3040","authenticated-orcid":false,"given":"Dale R.","family":"Nyholt","sequence":"additional","affiliation":[{"name":"Statistical and Genomic Epidemiology Laboratory, School of Biomedical Sciences, Faculty of Health, Centre for Genomics and Personalised Health, Queensland University of Technology, Kelvin Grove, QLD 4000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,12]]},"reference":[{"key":"ref_1","unstructured":"GBD 2016 Disease and Injury Incidence and Prevalence Collaborators (2017). Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990\u20132016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet, 390, 1211\u20131259."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1038\/s41588-021-00990-0","article-title":"Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles","volume":"54","author":"Hautakangas","year":"2022","journal-title":"Nat. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1038\/ng.3598","article-title":"Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine","volume":"48","author":"Gormley","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3368","DOI":"10.1038\/s41467-020-17002-0","article-title":"A genome-wide cross-phenotype meta-analysis of the association of blood pressure with migraine","volume":"11","author":"Guo","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1212\/NXG.0000000000000653","article-title":"Migraine, Stroke, and Cervical Arterial Dissection","volume":"8","author":"Daghlas","year":"2022","journal-title":"Neurol. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"i2610","DOI":"10.1136\/bmj.i2610","article-title":"Migraine and risk of cardiovascular disease in women: Prospective cohort study","volume":"353","author":"Kurth","year":"2016","journal-title":"BMJ"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"444","DOI":"10.4239\/wjd.v5.i4.444","article-title":"Type 2 diabetes and cardiovascular disease: Have all risk factors the same strength?","volume":"5","year":"2014","journal-title":"World J. Diabetes"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.1212\/WNL.0b013e3181a71220","article-title":"Migraine and cardiovascular disease: Possible mechanisms of interaction","volume":"72","author":"Bigal","year":"2009","journal-title":"Neurology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1136\/jnnp.2009.192492","article-title":"Sociodemographic and comorbidity profiles of chronic migraine and episodic migraine sufferers","volume":"81","author":"Buse","year":"2010","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1001\/jamaneurol.2018.3960","article-title":"Associations Between Migraine and Type 2 Diabetes in Women: Findings From the E3N Cohort Study","volume":"76","author":"Fagherazzi","year":"2019","journal-title":"JAMA Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Islam, M.R., and Nyholt, D.R. (2022). Glucose-Related Traits and Risk of Migraine-A Potential Mechanism and Treatment Consideration. Genes, 13.","DOI":"10.3390\/genes13050730"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1093\/ije\/dyaa050","article-title":"Cross-trait analyses with migraine reveal widespread pleiotropy and suggest a vascular component to migraine headache","volume":"49","author":"Siewert","year":"2020","journal-title":"Int. J. Epidemiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"107","DOI":"10.2991\/jegh.k.191028.001","article-title":"Epidemiology of Type 2 Diabetes\u2014Global Burden of Disease and Forecasted Trends","volume":"10","author":"Khan","year":"2020","journal-title":"J. Epidemiol. Glob. Health"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"87","DOI":"10.3390\/genes6010087","article-title":"Genetics of type 2 diabetes-pitfalls and possibilities","volume":"6","author":"Prasad","year":"2015","journal-title":"Genes"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1097\/WCO.0000000000000687","article-title":"Advance in genetics of migraine","volume":"32","author":"Terwindt","year":"2019","journal-title":"Curr. Opin. Neurol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.ebiom.2018.01.023","article-title":"A Genome-Wide Association Study Finds Genetic Associations with Broadly-Defined Headache in UK Biobank (N = 223,773)","volume":"28","author":"Meng","year":"2018","journal-title":"EBioMedicine"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1038\/s41588-018-0241-6","article-title":"Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps","volume":"50","author":"Mahajan","year":"2018","journal-title":"Nat. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/s43586-021-00056-9","article-title":"Genome-wide association studies","volume":"1","author":"Uffelmann","year":"2021","journal-title":"Nat. Rev. Methods Prim."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2546","DOI":"10.1093\/brain\/aws175","article-title":"Her versus his migraine: Multiple sex differences in brain function and structure","volume":"135","author":"Maleki","year":"2012","journal-title":"Brain"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1111\/head.12482","article-title":"The prevalence and burden of migraine and severe headache in the U nited S tates: Updated statistics from government health surveillance studies","volume":"55","author":"Burch","year":"2015","journal-title":"Headache J. Head Face Pain"},{"key":"ref_21","unstructured":"(2022, August 20). Neale Lab. Rapid GWAS of Thousands of Phenotypes for 337,000 Samples in the UK Biobank. Available online: http:\/\/www.nealelab.is\/blog\/2017\/7\/19\/rapid-gwas-of-thousands-of-phenotypes-for-337000-samples-in-the-uk-biobank."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1177\/0333102413485658","article-title":"The International Classification of Headache Disorders, 3rd edition (beta version)","volume":"33","author":"Zhang","year":"2013","journal-title":"Cephalalgia"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1038\/ng.2676","article-title":"Genome-wide meta-analysis identifies new susceptibility loci for migraine","volume":"45","author":"Anttila","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1111\/head.12150","article-title":"Sex Differences in the Prevalence, Symptoms, and Associated Features of Migraine, Probable Migraine and Other Severe Headache: Results of the American Migraine Prevalence and Prevention (AMPP) Study","volume":"53","author":"Buse","year":"2013","journal-title":"Headache J. Head Face Pain"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"549038","DOI":"10.3389\/fneur.2020.549038","article-title":"Giving Researchers a Headach\u2014Sex and Gender Differences in Migraine","volume":"11","author":"Haas","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2086","DOI":"10.1093\/bioinformatics\/btu171","article-title":"SECA: SNP effect concordance analysis using genome-wide association summary results","volume":"30","author":"Nyholt","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1038\/ng.3406","article-title":"An atlas of genetic correlations across human diseases and traits","volume":"47","author":"Finucane","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_28","unstructured":"GBD 2016 Headache Collaborators (2018). Global, regional, and national burden of migraine and tension-type headache, 1990\u20132016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet. Neurol., 17, 954\u2013976."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"107843","DOI":"10.1016\/j.diabres.2019.107843","article-title":"Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9(th) edition","volume":"157","author":"Saeedi","year":"2019","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1038\/ng.3570","article-title":"Detection and interpretation of shared genetic influences on 42 human traits","volume":"48","author":"Pickrell","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1016\/j.ajhg.2011.04.014","article-title":"Random-effects model aimed at discovering associations in meta-analysis of genome-wide association studies","volume":"88","author":"Han","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Han, B., and Eskin, E. (2012). Interpreting Meta-Analyses of Genome-Wide Association Studies. PLOS Genet., 8.","DOI":"10.1371\/journal.pgen.1002555"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1038\/s41467-017-01261-5","article-title":"Functional mapping and annotation of genetic associations with FUMA","volume":"8","author":"Watanabe","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/nature15393","article-title":"A global reference for human genetic variation","volume":"526","author":"Auton","year":"2015","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3207","DOI":"10.1093\/bioinformatics\/btw373","article-title":"PhenoScanner: A database of human genotype-phenotype associations","volume":"32","author":"Staley","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1177\/0333102415591497","article-title":"Gene-based pleiotropy across migraine with aura and migraine without aura patient groups","volume":"36","author":"Zhao","year":"2016","journal-title":"Cephalalgia Int. J. Headache"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.ajhg.2011.01.019","article-title":"GATES: A rapid and powerful gene-based association test using extended Simes procedure","volume":"88","author":"Li","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Chanda, P., Huang, H., Arking, D.E., and Bader, J.S. (2013). Fast association tests for genes with FAST. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0068585"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1007\/s00439-011-1118-2","article-title":"Evaluating the effective numbers of independent tests and significant p-value thresholds in commercial genotyping arrays and public imputation reference datasets","volume":"131","author":"Li","year":"2012","journal-title":"Hum. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Adewuyi, E.O., Sapkota, Y., Auta, A., Yoshihara, K., Nyegaard, M., Griffiths, L.R., Montgomery, G.W., International Endogene Consortium, 23andMe Research Team, and International Headache Genetics Consortium (2020). Shared Molecular Genetic Mechanisms Underlie Endometriosis and Migraine Comorbidity. Genes, 11.","DOI":"10.3390\/genes11030268"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1038\/s41431-018-0150-2","article-title":"Molecular genetic overlap between migraine and major depressive disorder","volume":"26","author":"Yang","year":"2018","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1007\/s00439-020-02223-6","article-title":"Genetic analysis of endometriosis and depression identifies shared loci and implicates causal links with gastric mucosa abnormality","volume":"140","author":"Adewuyi","year":"2021","journal-title":"Hum. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/s00439-016-1755-6","article-title":"Gene-based analyses reveal novel genetic overlap and allelic heterogeneity across five major psychiatric disorders","volume":"136","author":"Zhao","year":"2017","journal-title":"Hum. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e34408","DOI":"10.7554\/eLife.34408","article-title":"The MR-Base platform supports systematic causal inference across the human phenome","volume":"7","author":"Hemani","year":"2018","journal-title":"eLife"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/s41467-017-02317-2","article-title":"Causal associations between risk factors and common diseases inferred from GWAS summary data","volume":"9","author":"Zhu","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1093\/ije\/dyv080","article-title":"Mendelian randomization with invalid instruments: Effect estimation and bias detection through Egger regression","volume":"44","author":"Bowden","year":"2015","journal-title":"Int. J. Epidemiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1002\/gepi.21965","article-title":"Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator","volume":"40","author":"Bowden","year":"2016","journal-title":"Genet. Epidemiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/s41588-018-0099-7","article-title":"Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases","volume":"50","author":"Verbanck","year":"2018","journal-title":"Nat. Genet."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.ajhg.2010.11.011","article-title":"GCTA: A tool for genome-wide complex trait analysis","volume":"88","author":"Yang","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1038\/s41588-018-0255-0","article-title":"Distinguishing genetic correlation from causation across 52 diseases and complex traits","volume":"50","author":"Price","year":"2018","journal-title":"Nat. Genet."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"W83","DOI":"10.1093\/nar\/gkw199","article-title":"g:Profiler-a web server for functional interpretation of gene lists (2016 update)","volume":"44","author":"Reimand","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"W191","DOI":"10.1093\/nar\/gkz369","article-title":"g:Profiler: A web server for functional enrichment analysis and conversions of gene lists (2019 update)","volume":"47","author":"Raudvere","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_53","first-page":"327","article-title":"Headaches in non insulin-dependent diabetes mellitus","volume":"12","author":"Split","year":"1997","journal-title":"Funct. Neurol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1177\/0333102409355601","article-title":"Migraine prevalence by age and sex in the United States: A life-span study","volume":"30","author":"Victor","year":"2010","journal-title":"Cephalalgia"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1007\/s10072-020-04643-8","article-title":"Gender-related differences in migraine","volume":"41","author":"Allais","year":"2020","journal-title":"Neurol. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1186\/s13073-016-0332-x","article-title":"Genetic pleiotropy in complex traits and diseases: Implications for genomic medicine","volume":"8","author":"Gratten","year":"2016","journal-title":"Genome Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/s41588-020-0637-y","article-title":"Discovery of 318 new risk loci for type 2 diabetes and related vascular outcomes among 1.4 million participants in a multi-ancestry meta-analysis","volume":"52","author":"Vujkovic","year":"2020","journal-title":"Nat. Genet."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1038\/s41582-019-0216-y","article-title":"Does inflammation have a role in migraine?","volume":"15","author":"Edvinsson","year":"2019","journal-title":"Nat. Rev. Neurol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3812","DOI":"10.1038\/s41467-020-17468-y","article-title":"Targeting QKI-7 in vivo restores endothelial cell function in diabetes","volume":"11","author":"Yang","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.conb.2017.12.003","article-title":"NLGN1 and NLGN2 in the prefrontal cortex: Their role in memory consolidation and strengthening","volume":"48","author":"Katzman","year":"2018","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"4501","DOI":"10.1038\/ncomms5501","article-title":"Elfn1 recruits presynaptic mGluR7 in trans and its loss results in seizures","volume":"5","author":"Tomioka","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Dolan, J., and Mitchell, K.J. (2013). Mutation of Elfn1 in mice causes seizures and hyperactivity. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0080491"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1093\/brain\/awab267","article-title":"Dissecting the shared genetic basis of migraine and mental disorders using novel statistical tools","volume":"145","author":"Bahrami","year":"2022","journal-title":"Brain"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s10194-020-01109-2","article-title":"Brain morphologic abnormalities in migraine patients: An observational study","volume":"21","author":"Bonanno","year":"2020","journal-title":"J. Headache Pain"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"13384","DOI":"10.1073\/pnas.1906275116","article-title":"Genome-wide CRISPR screen identifies suppressors of endoplasmic reticulum stress-induced apoptosis","volume":"116","author":"Panganiban","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1083\/jcb.201008051","article-title":"Family-wide characterization of the DENN domain Rab GDP-GTP exchange factors","volume":"191","author":"Yoshimura","year":"2010","journal-title":"J. Cell Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.nbd.2017.01.005","article-title":"Neuroendocrine signaling modulates specific neural networks relevant to migraine","volume":"101","author":"Akerman","year":"2017","journal-title":"Neurobiol. Dis."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1177\/0333102413511155","article-title":"Insulin resistance in migraineurs: Results from a case-control study","volume":"34","author":"Sacco","year":"2014","journal-title":"Cephalalgia Int. J. Headache"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1038\/nrneurol.2017.151","article-title":"Migrainomics\u2014Identifying brain and genetic markers of migraine","volume":"13","author":"Nyholt","year":"2017","journal-title":"Nat. Rev. Neurol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1111\/j.1468-1331.2007.01765.x","article-title":"Headache prevalence related to diabetes mellitus. The Head-HUNT study","volume":"14","author":"Aamodt","year":"2007","journal-title":"Eur. J. Neurol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1177\/0333102417748573","article-title":"Diabetes is associated with decreased migraine risk: A nationwide cohort study","volume":"38","author":"Antonazzo","year":"2018","journal-title":"Cephalalgia Int. J. Headache"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1097\/EDE.0b013e31827623d0","article-title":"Does diabetes have a protective effect on migraine?","volume":"24","author":"Berge","year":"2013","journal-title":"J. Epidemiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1177\/147323001204000114","article-title":"Serum levels of calcitonin gene-related peptide and substance P are decreased in patients with diabetes mellitus and coronary artery disease","volume":"40","author":"Wang","year":"2012","journal-title":"J. Int. Med. Res."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Carmine Belin, A., Ran, C., and Edvinsson, L. (2020). Calcitonin Gene-Related Peptide (CGRP) and Cluster Headache. Brain Sci., 10.","DOI":"10.3390\/brainsci10010030"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.peptides.2017.08.007","article-title":"Association of down-regulation of calcitonin gene-related peptide and substance P with increase of myocardial vulnerability in diabetic neuropathic rats","volume":"96","author":"Li","year":"2017","journal-title":"Peptides"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1111\/j.1526-4610.2006.00483.x","article-title":"Calcitonin gene-related peptide (CGRP) and migraine","volume":"46","author":"Durham","year":"2006","journal-title":"Headache"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1007\/s001250100001","article-title":"Vascular factors and metabolic interactions in the pathogenesis of diabetic neuropathy","volume":"44","author":"Cameron","year":"2001","journal-title":"Diabetologia"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"5853","DOI":"10.1039\/D1SC01167G","article-title":"\u03b1-CGRP disrupts amylin fibrillization and regulates insulin secretion: Implications on diabetes and migraine","volume":"12","author":"Gray","year":"2021","journal-title":"Chem. Sci."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/10\/1845\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:53:00Z","timestamp":1760143980000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/10\/1845"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,12]]},"references-count":78,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["genes13101845"],"URL":"https:\/\/doi.org\/10.3390\/genes13101845","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,12]]}}}