An X Chromosome Association Scan of the Norfolk Island Genetic Isolate Provides Evidence for a Novel Migraine Susceptibility Locus at Xq12

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An X Chromosome Association Scan of the Norfolk Island Genetic Isolate Provides Evidence for a Novel Migraine Susceptibility Locus at Xq12

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Title: An X Chromosome Association Scan of the Norfolk Island Genetic Isolate Provides Evidence for a Novel Migraine Susceptibility Locus at Xq12
Author: Maher, Bridget H.; Lea, Rod A.; Benton, Miles; Cox, Hannah C.; Bellis, Claire; Carless, Melanie; Dyer, Thomas D.; Curran, Joanne; Charlesworth, Jac C.; Schürks, Markus; Blangero, John; Griffiths, Lyn R.; Buring, Julie Elizabeth; Kurth, Tobias; Chasman, Daniel Ian; Ridker, Paul M.

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Citation: Maher, Bridget H., Rod A. Lea, Miles Benton, Hannah C. Cox, Claire Bellis, Melanie Carless, Thomas D. Dyer, et al. 2012. An X chromosome association scan of the Norfolk Island genetic isolate provides evidence for a novel migraine susceptibility locus at Xq12. PLoS ONE 7(5): e37903.
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Abstract: Migraine 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 \(\alpha\) = 1×10\(^{−5}\)) 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 = 8.92×10\(^{−4}\)), whilst at Xq27 the strongest association was for rs6525667 (OR = 1.53, P = 1.65×10\(^{−4}\)). 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 = 1.63×10\(^{−5}\)) is located within the 5′UTR of the HEPH gene, which is involved in iron homeostasis in the brain and may represent a novel pathway for involvement in migraine pathogenesis.
Published Version: doi:10.1371/journal.pone.0037903
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3362572/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10406327
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