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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
Citation
Maher, BH and Lea, RA and Benton, M and Cox, HC and Bellis, C and Carless, M and Dyer, TD and Curran, J and Charlesworth, JC and Buring, JE and Kurth, T and Chasman, DI and Ridker, PM and Schurks, M and Blangero, J and Griffiths, LR, 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) Article e37903. ISSN 1932-6203 (2012) [Refereed Article]
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Copyright Statement
Licensed under Creative Commons Attribution 2.5 Generic (CC BY 2.5) http://creativecommons.org/licenses/by/2.5/
DOI: doi:10.1371/journal.pone.0037903
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 α = 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.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Keywords: | genomics, genetics, statistical genetics, neurogenetics |
| Research Division: | Biological Sciences |
| Research Group: | Genetics |
| Research Field: | Genomics |
| Objective Division: | Health |
| Objective Group: | Clinical Health (Organs, Diseases and Abnormal Conditions) |
| Objective Field: | Inherited Diseases (incl. Gene Therapy) |
| Author: | Charlesworth, JC (Dr Jac Charlesworth) |
| ID Code: | 78794 |
| Year Published: | 2012 |
| Web of Science® Times Cited: | 8 |
| Deposited By: | Menzies Institute for Medical Research |
| Deposited On: | 2012-07-26 |
| Last Modified: | 2013-04-16 |
| Downloads: | 0 |
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