%0 Journal Article
%T An X Chromosome Association Scan of the Norfolk Island Genetic Isolate Provides Evidence for a Novel Migraine Susceptibility Locus at Xq12
%A Bridget H. Maher
%A Rod A. Lea
%A Miles Benton
%A Hannah C. Cox
%A Claire Bellis
%A Melanie Carless
%A Thomas D. Dyer
%A Joanne Curran
%A Jac C. Charlesworth
%A Julie E. Buring
%A Tobias Kurth
%A Daniel I. Chasman
%A Paul M. Ridker
%A Markus Sch¨¹rks
%A John Blangero
%A Lyn R. Griffiths
%J PLOS ONE
%D 2012
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0037903
%X 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 ¦Á = 1¡Á10£¿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¡Á10£¿4), whilst at Xq27 the strongest association was for rs6525667 (OR = 1.53, P = 1.65¡Á10£¿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¡Á10£¿5) is located within the 5¡äUTR of the HEPH gene, which is involved in iron homeostasis in the brain and may represent a novel pathway for involvement in migraine pathogenesis.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0037903