Neurogenetics

, Volume 6, Issue 2, pp 67–72 | Cite as

A genome-wide scan provides evidence for loci influencing a severe heritable form of common migraine

  • R. A. Lea
  • D. R. Nyholt
  • R. P. Curtain
  • M. Ovcaric
  • R. Sciascia
  • C. Bellis
  • J. MacMillan
  • S. Quinlan
  • R. A. Gibson
  • L. C. McCarthy
  • J. H. Riley
  • Y. J. Smithies
  • S. Kinrade
  • L. R. Griffiths
Original Article

Abstract

Migraine is a prevalent neurovascular disease with a significant genetic component. Linkage studies have so far identified migraine susceptibility loci on chromosomes 1, 4, 6, 11, 14, 19 and X. We performed a genome-wide scan of 92 Australian pedigrees phenotyped for migraine with and without aura and for a more heritable form of “severe” migraine. Multipoint non-parametric linkage analysis revealed suggestive linkage on chromosome 18p11 for the severe migraine phenotype (LOD*=2.32, P=0.0006) and chromosome 3q (LOD*=2.28, P=0.0006). Excess allele sharing was also observed at multiple different chromosomal regions, some of which overlap with, or are directly adjacent to, previously implicated migraine susceptibility regions. We have provided evidence for two loci involved in severe migraine susceptibility and conclude that dissection of the “migraine” phenotype may be helpful for identifying susceptibility genes that influence the more heritable clinical (symptom) profiles in affected pedigrees. Also, we concluded that the genetic aetiology of the common (International Headache Society) forms of the disease is probably comprised of a number of low to moderate effect susceptibility genes, perhaps acting synergistically, and this effect is not easily detected by traditional single-locus linkage analyses of large samples of affected pedigrees.

Keywords

Migraine Susceptibility Genome scan Loci 

Notes

Acknowledgements

This research was supported by funding by GlaxoSmithKline and the National Health and Medical Research Council (NHMRC) of Australia. Dr. Rod Lea is supported by an NHMRC research fellowship (CJ Martin). The authors wish to thank Ralph McGinnis and Pam St Jean for statistical computing assistance and the GRC clinical staff and volunteers for aiding with collection and management of blood samples and pedigree data.

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • R. A. Lea
    • 1
    • 2
  • D. R. Nyholt
    • 3
  • R. P. Curtain
    • 1
  • M. Ovcaric
    • 1
  • R. Sciascia
    • 1
  • C. Bellis
    • 1
  • J. MacMillan
    • 4
  • S. Quinlan
    • 1
  • R. A. Gibson
    • 5
  • L. C. McCarthy
    • 5
  • J. H. Riley
    • 5
  • Y. J. Smithies
    • 6
  • S. Kinrade
    • 7
  • L. R. Griffiths
    • 1
  1. 1.Genomics Research Centre, School of Health ScienceGriffith UniversityQueenslandAustralia
  2. 2.Institute of Environmental Science and ResearchWellingtonNew Zealand
  3. 3.Genetic Epidemiology LaboratoryQueensland Institute of Medical ResearchHerstonAustralia
  4. 4.Queensland Clinical Genetics Service, Royal Children’s HospitalHerstonAustralia
  5. 5.GlaxoSmithKline Medicines Research CentreHertsUK
  6. 6.GlaxoSmithKlineMiddlesexUK
  7. 7.GlaxoSmithKline Pharmaceuticals DivisionVictoriaAustralia

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