Please use this identifier to cite or link to this item:
Title: An X Chromosome Association Scan of the Norfolk Island Genetic Isolate Provides Evidence for a Novel Migraine Susceptibility Locus at Xq12
Authors: 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.
subject: Biology;Computational Biology;Population Genetics;Genetic Polymorphism;Evolutionary Biology;Genetics;Genome-Wide Association Studies;Population Biology;Medicine;Neurology;Headaches;Migraine
Year: 2012
Publisher: Public Library of Science
Description: 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.
Standard no: 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.
Appears in Collections:HMS Scholarly Articles

Files in This Item:
Click on the URI links for accessing contents.

Items in HannanDL are protected by copyright, with all rights reserved, unless otherwise indicated.