{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,14]],"date-time":"2026-11-14T02:01:12Z","timestamp":1794621672216,"version":"4.9.1"},"reference-count":90,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T00:00:00Z","timestamp":1626912000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T00:00:00Z","timestamp":1626912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"NIH National Institute for Neurological Disorders and Stroke"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Migraine is a common disabling primary headache disorder that is ranked as the most common neurological cause of disability worldwide. Women present with migraine much more frequently than men, but the reasons for this difference are unknown. Migraine heritability is estimated to up to 57%, yet much of the genetic risk remains unaccounted for, especially in non-European ancestry populations. To elucidate the etiology of this common disorder, we conduct a multiethnic genome-wide association meta-analysis of migraine, combining results from the GERA and UK Biobank cohorts, followed by a European-ancestry meta-analysis using public summary statistics. We report 79 loci associated with migraine, of which 45 were novel. Sex-stratified analyses identify three additional novel loci (\n                    <jats:italic>CPS1<\/jats:italic>\n                    ,\n                    <jats:italic>PBRM1<\/jats:italic>\n                    , and\n                    <jats:italic>SLC25A21<\/jats:italic>\n                    ) specific to women. This large multiethnic migraine study provides important information that may substantially improve our understanding of the etiology of migraine susceptibility.\n                  <\/jats:p>","DOI":"10.1038\/s42003-021-02356-y","type":"journal-article","created":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T12:03:18Z","timestamp":1626955398000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["New and sex-specific migraine susceptibility loci identified from a multiethnic genome-wide meta-analysis"],"prefix":"10.1038","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9839-8667","authenticated-orcid":false,"given":"H\u00e9l\u00e8ne","family":"Choquet","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice S.","family":"Jacobson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon H.","family":"Horton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6893-4449","authenticated-orcid":false,"given":"Thomas J.","family":"Hoffmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5829-8191","authenticated-orcid":false,"given":"Eric","family":"Jorgenson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1723-7904","authenticated-orcid":false,"given":"Andrew L.","family":"Avins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2775-3275","authenticated-orcid":false,"given":"Alice R.","family":"Pressman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,22]]},"reference":[{"key":"2356_CR1","doi-asserted-by":"publisher","DOI":"10.1186\/1129-2377-14-1","volume":"14","author":"TJ Steiner","year":"2013","unstructured":"Steiner, T. J., Stovner, L. J. & Birbeck, G. L. Migraine: the seventh disabler. J. Headache Pain. 14, 1 (2013).","journal-title":"J. Headache Pain."},{"key":"2356_CR2","doi-asserted-by":"crossref","unstructured":"Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia 38, 1\u2013211 (2018).","DOI":"10.1177\/0333102417738202"},{"key":"2356_CR3","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1016\/S0140-6736(15)60692-4","volume":"386","author":"Global Burden of Disease Study 2013 Collaborators.","year":"2015","unstructured":"Global Burden of Disease Study 2013 Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990\u20132013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 386, 743\u2013800 (2015).","journal-title":"Lancet"},{"key":"2356_CR4","doi-asserted-by":"publisher","DOI":"10.1186\/1129-2377-15-6","volume":"15","author":"R Wang","year":"2014","unstructured":"Wang, R. et al. Gender differences of cognitive function in migraine patients: evidence from event-related potentials using the oddball paradigm. J. Headache Pain. 15, 6 (2014).","journal-title":"J. Headache Pain."},{"key":"2356_CR5","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1111\/j.1526-4610.2011.02061.x","volume":"52","author":"S Yu","year":"2012","unstructured":"Yu, S. et al. The prevalence and burden of primary headaches in China: a population-based door-to-door survey. Headache 52, 582\u2013591 (2012).","journal-title":"Headache"},{"key":"2356_CR6","doi-asserted-by":"publisher","first-page":"2546","DOI":"10.1093\/brain\/aws175","volume":"135","author":"N Maleki","year":"2012","unstructured":"Maleki, N. et al. Her versus his migraine: multiple sex differences in brain function and structure. Brain 135, 2546\u20132559 (2012).","journal-title":"Brain"},{"key":"2356_CR7","doi-asserted-by":"publisher","first-page":"e27049","DOI":"10.1371\/journal.pone.0027049","volume":"6","author":"J Liu","year":"2011","unstructured":"Liu, J. et al. Gender-related differences in the dysfunctional resting networks of migraine suffers. PLoS One 6, e27049 (2011).","journal-title":"PLoS One"},{"key":"2356_CR8","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1111\/head.12482","volume":"55","author":"RC Burch","year":"2015","unstructured":"Burch, R. C., Loder, S., Loder, E. & Smitherman, T. A. The prevalence and burden of migraine and severe headache in the United States: updated statistics from government health surveillance studies. Headache 55, 21\u201334 (2015).","journal-title":"Headache"},{"key":"2356_CR9","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1038\/ng.3285","volume":"47","author":"TJ Polderman","year":"2015","unstructured":"Polderman, T. J. et al. Meta-analysis of the heritability of human traits based on fifty years of twin studies. Nat. Genet. 47, 702\u2013709 (2015).","journal-title":"Nat. Genet."},{"key":"2356_CR10","doi-asserted-by":"publisher","first-page":"e1006711","DOI":"10.1371\/journal.pgen.1006711","volume":"13","author":"T Ge","year":"2017","unstructured":"Ge, T., Chen, C. Y., Neale, B. M., Sabuncu, M. R. & Smoller, J. W. Phenome-wide heritability analysis of the UK Biobank. PLoS Genet. 13, e1006711 (2017).","journal-title":"PLoS Genet."},{"key":"2356_CR11","doi-asserted-by":"publisher","first-page":"1202","DOI":"10.1038\/s41431-018-0150-2","volume":"26","author":"Y Yang","year":"2018","unstructured":"Yang, Y. et al. Molecular genetic overlap between migraine and major depressive disorder. Eur. J. Hum. Genet. 26, 1202\u20131216 (2018).","journal-title":"Eur. J. Hum. Genet."},{"key":"2356_CR12","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1046\/j.1526-4610.2003.03047.x","volume":"43","author":"DA Svensson","year":"2003","unstructured":"Svensson, D. A., Larsson, B., Waldenlind, E. & Pedersen, N. L. Shared rearing environment in migraine: results from twins reared apart and twins reared together. Headache 43, 235\u2013244 (2003).","journal-title":"Headache"},{"key":"2356_CR13","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1375\/136905203770326420","volume":"6","author":"EJ Mulder","year":"2003","unstructured":"Mulder, E. J. et al. Genetic and environmental influences on migraine: a twin study across six countries. Twin Res. 6, 422\u2013431 (2003).","journal-title":"Twin Res."},{"key":"2356_CR14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s10194-011-0399-0","volume":"13","author":"M Schurks","year":"2012","unstructured":"Schurks, M. Genetics of migraine in the age of genome-wide association studies. J. Headache Pain. 13, 1\u20139 (2012).","journal-title":"J. Headache Pain."},{"key":"2356_CR15","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.gene.2011.11.056","volume":"494","author":"HC Cox","year":"2012","unstructured":"Cox, H. C. et al. Heritability and genome-wide linkage analysis of migraine in the genetic isolate of Norfolk Island. Gene 494, 119\u2013123 (2012).","journal-title":"Gene"},{"key":"2356_CR16","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1111\/j.1526-4610.1995.hed3502070.x","volume":"35","author":"ML Honkasalo","year":"1995","unstructured":"Honkasalo, M. L. et al. Migraine and concomitant symptoms among 8167 adult twin pairs. Headache 35, 70\u201378 (1995).","journal-title":"Headache"},{"key":"2356_CR17","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1038\/ng.652","volume":"42","author":"V Anttila","year":"2010","unstructured":"Anttila, V. et al. Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1. Nat. Genet. 42, 869\u2013873 (2010).","journal-title":"Nat. Genet."},{"key":"2356_CR18","doi-asserted-by":"publisher","first-page":"912","DOI":"10.1038\/ng.2676","volume":"45","author":"V Anttila","year":"2013","unstructured":"Anttila, V. et al. Genome-wide meta-analysis identifies new susceptibility loci for migraine. Nat. Genet. 45, 912\u2013917 (2013).","journal-title":"Nat. Genet."},{"key":"2356_CR19","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1038\/ng.856","volume":"43","author":"DI Chasman","year":"2011","unstructured":"Chasman, D. I. et al. Genome-wide association study reveals three susceptibility loci for common migraine in the general population. Nat. Genet. 43, 695\u2013698 (2011).","journal-title":"Nat. Genet."},{"key":"2356_CR20","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1038\/ng.2307","volume":"44","author":"T Freilinger","year":"2012","unstructured":"Freilinger, T. et al. Genome-wide association analysis identifies susceptibility loci for migraine without aura. Nat. Genet. 44, 777\u2013782 (2012).","journal-title":"Nat. Genet."},{"key":"2356_CR21","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1038\/ng.3598","volume":"48","author":"P Gormley","year":"2016","unstructured":"Gormley, P. et al. Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine. Nat. Genet. 48, 856\u2013866 (2016).","journal-title":"Nat. Genet."},{"key":"2356_CR22","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1136\/jmedgenet-2018-105359","volume":"55","author":"X Chang","year":"2018","unstructured":"Chang, X. et al. Common variants at 5q33.1 predispose to migraine in African-American children. J. Med Genet. 55, 831\u2013836 (2018).","journal-title":"J. Med Genet."},{"key":"2356_CR23","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1038\/ng.2213","volume":"44","author":"J Yang","year":"2012","unstructured":"Yang, J. et al. Conditional and joint multiple-SNP analysis of GWAS summary statistics identifies additional variants influencing complex traits. Nat. Genet. 44, 369\u2013375 (2012). S1-3.","journal-title":"Nat. Genet."},{"key":"2356_CR24","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1534\/genetics.115.176107","volume":"200","author":"W Chen","year":"2015","unstructured":"Chen, W. et al. Fine mapping causal variants with an approximate bayesian method using marginal test statistics. Genetics 200, 719\u2013736 (2015).","journal-title":"Genetics"},{"key":"2356_CR25","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01261-5","volume":"8","author":"K Watanabe","year":"2017","unstructured":"Watanabe, K., Taskesen, E., van Bochoven, A. & Posthuma, D. Functional mapping and annotation of genetic associations with FUMA. Nat. Commun. 8, 1826 (2017).","journal-title":"Nat. Commun."},{"key":"2356_CR26","doi-asserted-by":"publisher","first-page":"e1004219","DOI":"10.1371\/journal.pcbi.1004219","volume":"11","author":"CA de Leeuw","year":"2015","unstructured":"de Leeuw, C. A., Mooij, J. M., Heskes, T. & Posthuma, D. MAGMA: generalized gene-set analysis of GWAS data. PLoS Comput Biol. 11, e1004219 (2015).","journal-title":"PLoS Comput Biol."},{"key":"2356_CR27","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6890","volume":"6","author":"TH Pers","year":"2015","unstructured":"Pers, T. H. et al. Biological interpretation of genome-wide association studies using predicted gene functions. Nat. Commun. 6, 5890 (2015).","journal-title":"Nat. Commun."},{"key":"2356_CR28","doi-asserted-by":"publisher","first-page":"12223","DOI":"10.1073\/pnas.91.25.12223","volume":"91","author":"G Sauvageau","year":"1994","unstructured":"Sauvageau, G. et al. Differential expression of homeobox genes in functionally distinct CD34+ subpopulations of human bone marrow cells. Proc. Natl Acad. Sci. USA. 91, 12223\u201312227 (1994).","journal-title":"Proc. Natl Acad. Sci. USA."},{"key":"2356_CR29","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1093\/emboj\/21.3.365","volume":"21","author":"M Manzanares","year":"2002","unstructured":"Manzanares, M. et al. Krox20 and kreisler co-operate in the transcriptional control of segmental expression of Hoxb3 in the developing hindbrain. EMBO J. 21, 365\u2013376 (2002).","journal-title":"EMBO J."},{"key":"2356_CR30","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1002\/dvdy.20347","volume":"233","author":"KK Chan","year":"2005","unstructured":"Chan, K. K. et al. Hoxb3 vagal neural crest-specific enhancer element for controlling enteric nervous system development. Dev. Dyn. 233, 473\u2013483 (2005).","journal-title":"Dev. Dyn."},{"key":"2356_CR31","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/0092-8674(93)90659-E","volume":"72","author":"MH Sham","year":"1993","unstructured":"Sham, M. H. et al. The zinc finger gene Krox20 regulates HoxB2 (Hox2.8) during hindbrain segmentation. Cell 72, 183\u2013196 (1993).","journal-title":"Cell"},{"key":"2356_CR32","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1002\/1097-0177(2000)9999:9999<::AID-DVDY1014>3.0.CO;2-I","volume":"218","author":"LG Komuves","year":"2000","unstructured":"Komuves, L. G. et al. Changes in HOXB6 homeodomain protein structure and localization during human epidermal development and differentiation. Dev. Dyn. 218, 636\u2013647 (2000).","journal-title":"Dev. Dyn."},{"key":"2356_CR33","doi-asserted-by":"publisher","first-page":"2700","DOI":"10.1093\/hmg\/ddv028","volume":"24","author":"BS Hromatka","year":"2015","unstructured":"Hromatka, B. S. et al. Genetic variants associated with motion sickness point to roles for inner ear development, neurological processes and glucose homeostasis. Hum. Mol. Genet. 24, 2700\u20132708 (2015).","journal-title":"Hum. Mol. Genet."},{"key":"2356_CR34","doi-asserted-by":"publisher","first-page":"1224","DOI":"10.1111\/j.1526-4610.2005.00246.x","volume":"45","author":"K Ishizaki","year":"2005","unstructured":"Ishizaki, K. et al. Increased plasma transforming growth factor-beta1 in migraine. Headache 45, 1224\u20131228 (2005).","journal-title":"Headache"},{"key":"2356_CR35","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1177\/0883073814527163","volume":"30","author":"S Saygi","year":"2015","unstructured":"Saygi, S. et al. TGF-beta1 genotype in pediatric migraine patients. J. Child Neurol. 30, 27\u201331 (2015).","journal-title":"J. Child Neurol."},{"key":"2356_CR36","doi-asserted-by":"publisher","first-page":"4084","DOI":"10.1182\/blood.V91.11.4084","volume":"91","author":"B Varnum-Finney","year":"1998","unstructured":"Varnum-Finney, B. et al. The Notch ligand, Jagged-1, influences the development of primitive hematopoietic precursor cells. Blood 91, 4084\u20134091 (1998).","journal-title":"Blood"},{"key":"2356_CR37","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1002\/stem.170162","volume":"17","author":"L Walker","year":"1999","unstructured":"Walker, L. et al. The Notch\/Jagged pathway inhibits proliferation of human hematopoietic progenitors in vitro. Stem Cells 17, 162\u2013171 (1999).","journal-title":"Stem Cells"},{"key":"2356_CR38","doi-asserted-by":"publisher","first-page":"1365","DOI":"10.1084\/jem.192.9.1365","volume":"192","author":"FN Karanu","year":"2000","unstructured":"Karanu, F. N. et al. The notch ligand jagged-1 represents a novel growth factor of human hematopoietic stem cells. J. Exp. Med. 192, 1365\u20131372 (2000).","journal-title":"J. Exp. Med."},{"key":"2356_CR39","doi-asserted-by":"publisher","first-page":"e107175","DOI":"10.1371\/journal.pone.0107175","volume":"9","author":"GC Elliott","year":"2014","unstructured":"Elliott, G. C., Gurtu, R., McCollum, C., Newman, W. G. & Wang, T. Foramen ovale closure is a process of endothelial-to-mesenchymal transition leading to fibrosis. PLoS One 9, e107175 (2014).","journal-title":"PLoS One"},{"key":"2356_CR40","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1159\/000047758","volume":"13","author":"R Sztajzel","year":"2002","unstructured":"Sztajzel, R., Genoud, D., Roth, S., Mermillod, B. & Le Floch-Rohr, J. Patent foramen ovale, a possible cause of symptomatic migraine: a study of 74 patients with acute ischemic stroke. Cerebrovasc. Dis. 13, 102\u2013106 (2002).","journal-title":"Cerebrovasc. Dis."},{"key":"2356_CR41","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1177\/0333102414547784","volume":"35","author":"DR Nyholt","year":"2015","unstructured":"Nyholt, D. R. et al. Concordance of genetic risk across migraine subgroups: impact on current and future genetic association studies. Cephalalgia 35, 489\u2013499 (2015).","journal-title":"Cephalalgia"},{"key":"2356_CR42","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1016\/j.biopsych.2012.02.040","volume":"72","author":"E Vassos","year":"2012","unstructured":"Vassos, E. et al. Replication study and meta-analysis in European samples supports association of the 3p21.1 locus with bipolar disorder. Biol. Psychiatry 72, 645\u2013650 (2012).","journal-title":"Biol. Psychiatry"},{"key":"2356_CR43","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1038\/s41380-019-0592-0","volume":"25","author":"Z Yang","year":"2020","unstructured":"Yang, Z. et al. The genome-wide risk alleles for psychiatric disorders at 3p21.1 show convergent effects on mRNA expression, cognitive function, and mushroom dendritic spine. Mol. Psychiatry 25, 48\u201366 (2020).","journal-title":"Mol. Psychiatry"},{"key":"2356_CR44","doi-asserted-by":"publisher","first-page":"7501","DOI":"10.1073\/pnas.0813386106","volume":"106","author":"LJ Scott","year":"2009","unstructured":"Scott, L. J. et al. Genome-wide association and meta-analysis of bipolar disorder in individuals of European ancestry. Proc. Natl Acad. Sci. USA. 106, 7501\u20137506 (2009).","journal-title":"Proc. Natl Acad. Sci. USA."},{"key":"2356_CR45","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1038\/ng.523","volume":"42","author":"FJ McMahon","year":"2010","unstructured":"McMahon, F. J. et al. Meta-analysis of genome-wide association data identifies a risk locus for major mood disorders on 3p21.1. Nat. Genet. 42, 128\u2013131 (2010).","journal-title":"Nat. Genet."},{"key":"2356_CR46","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1093\/hmg\/ddq471","volume":"20","author":"HJ Williams","year":"2011","unstructured":"Williams, H. J. et al. Most genome-wide significant susceptibility loci for schizophrenia and bipolar disorder reported to date cross-traditional diagnostic boundaries. Hum. Mol. Genet. 20, 387\u2013391 (2011).","journal-title":"Hum. Mol. Genet."},{"key":"2356_CR47","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1016\/j.schres.2010.09.002","volume":"124","author":"KS Wang","year":"2010","unstructured":"Wang, K. S., Liu, X. F. & Aragam, N. A genome-wide meta-analysis identifies novel loci associated with schizophrenia and bipolar disorder. Schizophr. Res. 124, 192\u2013199 (2010).","journal-title":"Schizophr. Res."},{"key":"2356_CR48","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.scr.2018.05.013","volume":"30","author":"Y Arioka","year":"2018","unstructured":"Arioka, Y., Kushima, I., Kubo, H., Mori, D. & Ozaki, N. Induced pluripotent stem cells derived from a schizophrenia patient with ASTN2 deletion. Stem Cell Res. 30, 81\u201384 (2018).","journal-title":"Stem Cell Res."},{"key":"2356_CR49","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s11689-016-9170-9","volume":"8","author":"MJ Gazzellone","year":"2016","unstructured":"Gazzellone, M. J. et al. Uncovering obsessive-compulsive disorder risk genes in a pediatric cohort by high-resolution analysis of copy number variation. J. Neurodev. Disord. 8, 36 (2016).","journal-title":"J. Neurodev. Disord."},{"key":"2356_CR50","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1093\/ije\/dyaa050","volume":"49","author":"KM Siewert","year":"2020","unstructured":"Siewert, K. M. et al. Cross-trait analyses with migraine reveal widespread pleiotropy and suggest a vascular component to migraine headache. Int J. Epidemiol. 49, 1022\u20131031 (2020).","journal-title":"Int J. Epidemiol."},{"key":"2356_CR51","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17376-1","volume":"11","author":"T Elvsashagen","year":"2020","unstructured":"Elvsashagen, T. et al. The genetic architecture of human brainstem structures and their involvement in common brain disorders. Nat. Commun. 11, 4016 (2020).","journal-title":"Nat. Commun."},{"key":"2356_CR52","doi-asserted-by":"publisher","first-page":"393","DOI":"10.3389\/fpsyt.2020.00393","volume":"11","author":"R Schmidt-Kastner","year":"2020","unstructured":"Schmidt-Kastner, R., Guloksuz, S., Kietzmann, T., van Os, J. & Rutten, B. P. F. Analysis of GWAS-derived schizophrenia genes for links to ischemia-hypoxia response of the brain. Front Psychiatry 11, 393 (2020).","journal-title":"Front Psychiatry"},{"key":"2356_CR53","doi-asserted-by":"publisher","first-page":"623","DOI":"10.3892\/etm.2020.8717","volume":"20","author":"J Xu","year":"2020","unstructured":"Xu, J., Zhang, A. & Huang, F. Biallelic mutations in carbamoyl phosphate synthetase 1 induced hyperammonemia in a neonate: a case report. Exp. Ther. Med. 20, 623\u2013629 (2020).","journal-title":"Exp. Ther. Med."},{"key":"2356_CR54","doi-asserted-by":"publisher","first-page":"1717","DOI":"10.1016\/j.ymthe.2020.04.011","volume":"28","author":"M Nitzahn","year":"2020","unstructured":"Nitzahn, M. et al. Split AAV-mediated gene therapy restores ureagenesis in a murine model of carbamoyl phosphate synthetase 1 deficiency. Mol. Ther. 28, 1717\u20131730 (2020).","journal-title":"Mol. Ther."},{"key":"2356_CR55","doi-asserted-by":"publisher","first-page":"e23124","DOI":"10.1002\/jcla.23124","volume":"34","author":"L Fan","year":"2020","unstructured":"Fan, L. et al. Molecular, biochemical, and clinical analyses of five patients with carbamoyl phosphate synthetase 1 deficiency. J. Clin. Lab Anal. 34, e23124 (2020).","journal-title":"J. Clin. Lab Anal."},{"key":"2356_CR56","doi-asserted-by":"publisher","first-page":"1192","DOI":"10.1002\/jimd.12100","volume":"42","author":"J Haberle","year":"2019","unstructured":"Haberle, J. et al. Suggested guidelines for the diagnosis and management of urea cycle disorders: first revision. J. Inherit. Metab. Dis. 42, 1192\u20131230 (2019).","journal-title":"J. Inherit. Metab. Dis."},{"key":"2356_CR57","doi-asserted-by":"publisher","first-page":"5690915","DOI":"10.1155\/2020\/5690915","volume":"2020","author":"Q Zhou","year":"2020","unstructured":"Zhou, Q., Huang, H., Ma, L. & Zhu, T. The application of next-generation sequencing (NGS) in neonatal-onset urea cycle disorders (UCDs): clinical course, metabolomic profiling, and genetic findings in nine chinese hyperammonemia patients. Biomed. Res Int. 2020, 5690915 (2020).","journal-title":"Biomed. Res Int."},{"key":"2356_CR58","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.ymgme.2017.07.004","volume":"122","author":"P Scarcia","year":"2017","unstructured":"Scarcia, P., Palmieri, L., Agrimi, G., Palmieri, F. & Rottensteiner, H. Three mitochondrial transporters of Saccharomyces cerevisiae are essential for ammonium fixation and lysine biosynthesis in synthetic minimal medium. Mol. Genet Metab. 122, 54\u201360 (2017).","journal-title":"Mol. Genet Metab."},{"key":"2356_CR59","doi-asserted-by":"publisher","first-page":"2554","DOI":"10.1002\/ajmg.a.60677","volume":"176","author":"LH Rodan","year":"2018","unstructured":"Rodan, L. H. et al. Gain-of-function variants in the ODC1 gene cause a syndromic neurodevelopmental disorder associated with macrocephaly, alopecia, dysmorphic features, and neuroimaging abnormalities. Am. J. Med Genet A. 176, 2554\u20132560 (2018).","journal-title":"Am. J. Med Genet A."},{"key":"2356_CR60","doi-asserted-by":"publisher","first-page":"2548","DOI":"10.1002\/ajmg.a.40523","volume":"176","author":"CP Bupp","year":"2018","unstructured":"Bupp, C. P., Schultz, C. R., Uhl, K. L., Rajasekaran, S. & Bachmann, A. S. Novel de novo pathogenic variant in the ODC1 gene in a girl with developmental delay, alopecia, and dysmorphic features. Am. J. Med Genet A. 176, 2548\u20132553 (2018).","journal-title":"Am. J. Med Genet A."},{"key":"2356_CR61","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1038\/mp.2016.20","volume":"22","author":"CC Minica","year":"2017","unstructured":"Minica, C. C. et al. Pathways to smoking behaviours: biological insights from the Tobacco and Genetics Consortium meta-analysis. Mol. Psychiatry 22, 82\u201388 (2017).","journal-title":"Mol. Psychiatry"},{"key":"2356_CR62","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.3233\/JAD-140054","volume":"41","author":"J Sun","year":"2014","unstructured":"Sun, J. et al. Hidden risk genes with high-order intragenic epistasis in Alzheimer\u2019s disease. J. Alzheimers Dis. 41, 1039\u20131056 (2014).","journal-title":"J. Alzheimers Dis."},{"key":"2356_CR63","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/S0149-7634(96)00023-1","volume":"21","author":"D van Rossum","year":"1997","unstructured":"van Rossum, D., Hanisch, U. K. & Quirion, R. Neuroanatomical localization, pharmacological characterization and functions of CGRP, related peptides and their receptors. Neurosci. Biobehav Rev. 21, 649\u2013678 (1997).","journal-title":"Neurosci. Biobehav Rev."},{"key":"2356_CR64","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1146\/annurev-pharmtox-010814-124701","volume":"55","author":"AF Russo","year":"2015","unstructured":"Russo, A. F. Calcitonin gene-related peptide (CGRP): a new target for migraine. Annu Rev. Pharm. Toxicol. 55, 533\u2013552 (2015).","journal-title":"Annu Rev. Pharm. Toxicol."},{"key":"2356_CR65","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1002\/cpdd.345","volume":"6","author":"L Pellesi","year":"2017","unstructured":"Pellesi, L., Guerzoni, S. & Pini, L. A. Spotlight on anti-CGRP monoclonal antibodies in migraine: the clinical evidence to date. Clin. Pharm. Drug Dev. 6, 534\u2013547 (2017).","journal-title":"Clin. Pharm. Drug Dev."},{"key":"2356_CR66","doi-asserted-by":"publisher","first-page":"1719","DOI":"10.1016\/j.cell.2018.11.049","volume":"175","author":"L Edvinsson","year":"2018","unstructured":"Edvinsson, L. CGRP antibodies as prophylaxis in migraine. Cell 175, 1719 (2018).","journal-title":"Cell"},{"key":"2356_CR67","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1038\/s41582-018-0003-1","volume":"14","author":"L Edvinsson","year":"2018","unstructured":"Edvinsson, L., Haanes, K. A., Warfvinge, K. & Krause, D. N. CGRP as the target of new migraine therapies \u2013 successful translation from bench to clinic. Nat. Rev. Neurol. 14, 338\u2013350 (2018).","journal-title":"Nat. Rev. Neurol."},{"key":"2356_CR68","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1021\/acsptsci.9b00061","volume":"2","author":"CT King","year":"2019","unstructured":"King, C. T. et al. Discovery of the migraine prevention therapeutic aimovig (Erenumab), the first FDA-approved antibody against a G-protein-coupled receptor. ACS Pharm. Transl. Sci. 2, 485\u2013490 (2019).","journal-title":"ACS Pharm. Transl. Sci."},{"issue":"Suppl 3","key":"2356_CR69","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1111\/head.13379","volume":"58","author":"SJ Tepper","year":"2018","unstructured":"Tepper, S. J. History and review of anti-calcitonin gene-related peptide (CGRP) therapies: from translational research to treatment. Headache 58(Suppl 3), 238\u2013275 (2018).","journal-title":"Headache"},{"key":"2356_CR70","doi-asserted-by":"publisher","first-page":"854","DOI":"10.1136\/gutjnl-2018-317619","volume":"68","author":"C Schafmayer","year":"2019","unstructured":"Schafmayer, C. et al. Genome-wide association analysis of diverticular disease points towards neuromuscular, connective tissue and epithelial pathomechanisms. Gut 68, 854\u2013865 (2019).","journal-title":"Gut"},{"key":"2356_CR71","doi-asserted-by":"publisher","first-page":"4790254","DOI":"10.1155\/2020\/4790254","volume":"2020","author":"A El-Metwally","year":"2020","unstructured":"El-Metwally, A. et al. The epidemiology of migraine headache in Arab countries: a systematic review. ScientificWorldJournal 2020, 4790254 (2020).","journal-title":"ScientificWorldJournal"},{"key":"2356_CR72","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s10194-020-1078-9","volume":"21","author":"M Arzani","year":"2020","unstructured":"Arzani, M. et al. Gut-brain Axis and migraine headache: a comprehensive review. J. Headache Pain. 21, 15 (2020).","journal-title":"J. Headache Pain."},{"key":"2356_CR73","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1111\/j.1468-2982.2005.00997.x","volume":"26","author":"RB Leistad","year":"2006","unstructured":"Leistad, R. B., Sand, T., Westgaard, R. H., Nilsen, K. B. & Stovner, L. J. Stress-induced pain and muscle activity in patients with migraine and tension-type headache. Cephalalgia 26, 64\u201373 (2006).","journal-title":"Cephalalgia"},{"key":"2356_CR74","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1177\/0333102415590242","volume":"36","author":"A Pressman","year":"2016","unstructured":"Pressman, A. et al. Prevalence of migraine in a diverse community\u2013electronic methods for migraine ascertainment in a large integrated health plan. Cephalalgia 36, 325\u2013334 (2016).","journal-title":"Cephalalgia"},{"key":"2356_CR75","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1534\/genetics.115.178616","volume":"200","author":"Y Banda","year":"2015","unstructured":"Banda, Y. et al. Characterizing race\/ethnicity and genetic ancestry for 100,000 subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. Genetics 200, 1285\u20131295 (2015).","journal-title":"Genetics"},{"key":"2356_CR76","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1534\/genetics.115.178905","volume":"200","author":"MN Kvale","year":"2015","unstructured":"Kvale, M. N. et al. Genotyping informatics and quality control for 100,000 subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. Genetics 200, 1051\u20131060 (2015).","journal-title":"Genetics"},{"key":"2356_CR77","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.ygeno.2011.04.005","volume":"98","author":"TJ Hoffmann","year":"2011","unstructured":"Hoffmann, T. J. et al. Next generation genome-wide association tool: design and coverage of a high-throughput European-optimized SNP array. Genomics 98, 79\u201389 (2011).","journal-title":"Genomics"},{"key":"2356_CR78","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1016\/j.ygeno.2011.08.007","volume":"98","author":"TJ Hoffmann","year":"2011","unstructured":"Hoffmann, T. J. et al. Design and coverage of high throughput genotyping arrays optimized for individuals of East Asian, African American, and Latino race\/ethnicity using imputation and a novel hybrid SNP selection algorithm. Genomics 98, 422\u2013430 (2011).","journal-title":"Genomics"},{"key":"2356_CR79","doi-asserted-by":"publisher","first-page":"1443","DOI":"10.1038\/ng.3679","volume":"48","author":"PR Loh","year":"2016","unstructured":"Loh, P. R. et al. Reference-based phasing using the Haplotype Reference Consortium panel. Nat. Genet. 48, 1443\u20131448 (2016).","journal-title":"Nat. Genet."},{"key":"2356_CR80","doi-asserted-by":"publisher","first-page":"1284","DOI":"10.1038\/ng.3656","volume":"48","author":"S Das","year":"2016","unstructured":"Das, S. et al. Next-generation genotype imputation service and methods. Nat. Genet. 48, 1284\u20131287 (2016).","journal-title":"Nat. Genet."},{"key":"2356_CR81","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1038\/ng.3643","volume":"48","author":"S McCarthy","year":"2016","unstructured":"McCarthy, S. et al. A reference panel of 64,976 haplotypes for genotype imputation. Nat. Genet. 48, 1279\u20131283 (2016).","journal-title":"Nat. Genet."},{"key":"2356_CR82","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1038\/526052a","volume":"526","author":"E Birney","year":"2015","unstructured":"Birney, E. & Soranzo, N. Human genomics: the end of the start for population sequencing. Nature 526, 52\u201353 (2015).","journal-title":"Nature"},{"key":"2356_CR83","doi-asserted-by":"publisher","first-page":"e1001779","DOI":"10.1371\/journal.pmed.1001779","volume":"12","author":"C Sudlow","year":"2015","unstructured":"Sudlow, C. et al. UK Biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med. 12, e1001779 (2015).","journal-title":"PLoS Med."},{"key":"2356_CR84","doi-asserted-by":"publisher","first-page":"224ed4","DOI":"10.1126\/scitranslmed.3008601","volume":"6","author":"NE Allen","year":"2014","unstructured":"Allen, N. E., Sudlow, C., Peakman, T., Collins, R. & Biobank, U. K. UK biobank data: come and get it. Sci. Transl. Med. 6, 224ed4 (2014).","journal-title":"Sci. Transl. Med."},{"key":"2356_CR85","doi-asserted-by":"publisher","DOI":"10.1186\/s13742-015-0047-8","volume":"4","author":"CC Chang","year":"2015","unstructured":"Chang, C. C. et al. Second-generation PLINK: rising to the challenge of larger and richer datasets. Gigascience 4, 7 (2015).","journal-title":"Gigascience"},{"key":"2356_CR86","doi-asserted-by":"publisher","first-page":"904","DOI":"10.1038\/ng1847","volume":"38","author":"AL Price","year":"2006","unstructured":"Price, A. L. et al. Principal components analysis corrects for stratification in genome-wide association studies. Nat. Genet. 38, 904\u2013909 (2006).","journal-title":"Nat. Genet."},{"key":"2356_CR87","doi-asserted-by":"crossref","unstructured":"Mbatchou J. et al. Computationally efficient whole genome regression for quantitative and binary traits. bioRxiv. 2020:2020.06.19.162354.","DOI":"10.1101\/2020.06.19.162354"},{"key":"2356_CR88","unstructured":"R: A Language and Environment for Statistical Computing. The R Foundation for Statistical Computing. 2014."},{"key":"2356_CR89","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1126\/science.1262110","volume":"348","author":"GTEx Consortium.","year":"2015","unstructured":"GTEx Consortium. Human genomics. The Genotype-Tissue Expression (GTEx) pilot analysis: multitissue gene regulation in humans. Science 348, 648\u2013660 (2015).","journal-title":"Science"},{"key":"2356_CR90","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1093\/bioinformatics\/btw613","volume":"33","author":"J Zheng","year":"2017","unstructured":"Zheng, J. et al. LD Hub: a centralized database and web interface to perform LD score regression that maximizes the potential of summary level GWAS data for SNP heritability and genetic correlation analysis. Bioinformatics 33, 272\u2013279 (2017).","journal-title":"Bioinformatics"}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-021-02356-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-021-02356-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-021-02356-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,4]],"date-time":"2023-02-04T18:09:10Z","timestamp":1675534150000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-021-02356-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,22]]},"references-count":90,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["2356"],"URL":"https:\/\/doi.org\/10.1038\/s42003-021-02356-y","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,22]]},"assertion":[{"value":"21 October 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 June 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 July 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"H.C. is an Editorial Board Member for <i>Communications Biology<\/i>, but was not involved in the editorial review of, or the decision to publish this article. The authors declare no other competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"864"}}