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dc.contributor.authorMaher, Bridgeten_US
dc.contributor.authorLea, Rodneyen_US
dc.contributor.authorBenton, Milesen_US
dc.contributor.authorCox, Hannahen_US
dc.contributor.authorBellis, Claireen_US
dc.contributor.authorCarless, Melanieen_US
dc.contributor.authorD. Dyer, Thomasen_US
dc.contributor.authorCurran, Joanneen_US
dc.contributor.authorC. Charlesworth, Jacen_US
dc.contributor.authorE. Buring, Julieen_US
dc.contributor.authorKurth, Tobiasen_US
dc.contributor.authorI. Chasman, Danielen_US
dc.contributor.authorRidker, Paulen_US
dc.contributor.authorSchurks, Markusen_US
dc.contributor.authorBlangero, Johnen_US
dc.contributor.authorGriffiths, Lynen_US
dc.date.accessioned2017-04-24T08:34:12Z
dc.date.available2017-04-24T08:34:12Z
dc.date.issued2012en_US
dc.date.modified2013-06-17T03:24:50Z
dc.identifier.issn19326203en_US
dc.identifier.doi10.1371/journal.pone.0037903en_US
dc.identifier.urihttp://hdl.handle.net/10072/47748
dc.description.abstractMigraine is a common and debilitating neurovascular disorder with a complex envirogenomic aetiology. Numerous studies have demonstrated a preponderance of women affected with migraine and previous pedigree linkage studies in our laboratory have identified susceptibility loci on chromosome Xq24-Xq28. In this study we have used the genetic isolate of Norfolk Island to further analyse the X chromosome for migraine susceptibility loci. An association approach was employed to analyse 14,124 SNPs spanning the entire X chromosome. Genotype data from 288 individuals comprising a large core-pedigree, of which 76 were affected with migraine, were analysed. Although no SNP reached chromosome-wide significance (empirical a=161025) ranking by P-value revealed two primary clusters of SNPs in the top 25. A 10 SNP cluster represents a novel migraine susceptibility locus at Xq12 whilst a 11 SNP cluster represents a previously identified migraine susceptibility locus at Xq27. The strongest association at Xq12 was seen for rs599958 (OR = 1.75, P = 8.9261024), whilst at Xq27 the strongest association was for rs6525667 (OR = 1.53, P = 1.6561024). Further analysis of SNPs at these loci was performed in 5,122 migraineurs from the Women's Genome Health Study and provided additional evidence for association at the novel Xq12 locus (P,0.05). Overall, this study provides evidence for a novel migraine susceptibility locus on Xq12. The strongest effect SNP (rs102834, joint P = 1.6361025) is located within the 59UTR of the HEPH gene, which is involved in iron homeostasis in the brain and may represent a novel pathway for involvement in migraine pathogenesis.en_US
dc.description.peerreviewedYesen_US
dc.description.publicationstatusYesen_US
dc.format.extent703584 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglishen_US
dc.language.isoen_US
dc.publisherPublic Library of Scienceen_US
dc.publisher.placeUnited Statesen_US
dc.relation.ispartofstudentpublicationNen_US
dc.relation.ispartofpagefrome37903-1en_US
dc.relation.ispartofpagetoe37903-7en_US
dc.relation.ispartofissue5en_US
dc.relation.ispartofjournalPloS Oneen_US
dc.relation.ispartofvolume7en_US
dc.rights.retentionYen_US
dc.subject.fieldofresearchMedical and Health Sciences not elsewhere classifieden_US
dc.subject.fieldofresearchcode119999en_US
dc.titleAn X Chromosome Association Scan of the Norfolk Island Genetic Isolate Provides Evidence for a Novel Migraine Susceptibility Locus at Xq12en_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.facultyGriffith Health, School of Medical Scienceen_US
gro.rights.copyrightCopyright 2012 Maher et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License CCAL. (http://www.plos.org/journals/license.html)en_US
gro.date.issued2012
gro.hasfulltextFull Text


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