A genome-wide analysis of 'Bounty' descendants implicates several novel variants in migraine susceptibility

Hannah C. Cox, Rod A. Lea, Claire Bellis, Melanie Carless, Thomas D. Dyer, Joanne Curran, Jac Charlesworth, Stuart MacGregor, Dale Nyholt, Daniel Chasman, Paul M. Ridker, Markus Schürks, John Blangero, Lyn R. Griffiths

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Migraine is a common neurological disease with a complex genetic aetiology. The disease affects ~12∈% of the Caucasian population and females are three times more likely than males to be diagnosed. In an effort to identify loci involved in migraine susceptibility, we performed a pedigree-based genome-wide association study of the isolated population of Norfolk Island, which has a high prevalence of migraine. This unique population originates from a small number of British and Polynesian founders who are descendents of the Bounty mutiny and forms a very large multigenerational pedigree (Bellis et al.; Human Genetics, 124(5):543-5542, 2008). These population genetic features may facilitate disease gene mapping strategies (Peltonen et al.; Nat Rev Genet, 1(3):182-90, 2000. In this study, we identified a high heritability of migraine in the Norfolk Island population (h 2∈=∈0.53, P∈=∈0.016). We performed a pedigree-based GWAS and utilised a statistical and pathological prioritisation approach to implicate a number of variants in migraine. An SNP located in the zinc finger protein 555 (ZNF555) gene (rs4807347) showed evidence of statistical association in our Norfolk Island pedigree (P∈=∈9.6∈×∈10-6) as well as replication in a large independent and unrelated cohort with >500 migraineurs. In addition, we utilised a biological prioritisation to implicate four SNPs, in within the ADARB2 gene, two SNPs within the GRM7 gene and a single SNP in close proximity to a HTR7 gene. Association of SNPs within these neurotransmitter-related genes suggests a disrupted serotoninergic system that is perhaps specific to the Norfolk Island pedigree, but that might provide clues to understanding migraine more generally.

Original languageEnglish (US)
Pages (from-to)261-266
Number of pages6
JournalNeurogenetics
Volume13
Issue number3
DOIs
StatePublished - Aug 2012
Externally publishedYes

Fingerprint

Melanesia
Migraine Disorders
Pedigree
Single Nucleotide Polymorphism
Genome
Genome-Wide Association Study
Population
Genes
Viverridae
Chromosome Mapping
Zinc Fingers
Medical Genetics
Population Genetics
Neurotransmitter Agents
Proteins

Keywords

  • Association
  • Gene
  • Migraine

ASJC Scopus subject areas

  • Genetics(clinical)
  • Cellular and Molecular Neuroscience
  • Genetics

Cite this

Cox, H. C., Lea, R. A., Bellis, C., Carless, M., Dyer, T. D., Curran, J., ... Griffiths, L. R. (2012). A genome-wide analysis of 'Bounty' descendants implicates several novel variants in migraine susceptibility. Neurogenetics, 13(3), 261-266. https://doi.org/10.1007/s10048-012-0325-x

A genome-wide analysis of 'Bounty' descendants implicates several novel variants in migraine susceptibility. / Cox, Hannah C.; Lea, Rod A.; Bellis, Claire; Carless, Melanie; Dyer, Thomas D.; Curran, Joanne; Charlesworth, Jac; MacGregor, Stuart; Nyholt, Dale; Chasman, Daniel; Ridker, Paul M.; Schürks, Markus; Blangero, John; Griffiths, Lyn R.

In: Neurogenetics, Vol. 13, No. 3, 08.2012, p. 261-266.

Research output: Contribution to journalArticle

Cox, HC, Lea, RA, Bellis, C, Carless, M, Dyer, TD, Curran, J, Charlesworth, J, MacGregor, S, Nyholt, D, Chasman, D, Ridker, PM, Schürks, M, Blangero, J & Griffiths, LR 2012, 'A genome-wide analysis of 'Bounty' descendants implicates several novel variants in migraine susceptibility', Neurogenetics, vol. 13, no. 3, pp. 261-266. https://doi.org/10.1007/s10048-012-0325-x
Cox, Hannah C. ; Lea, Rod A. ; Bellis, Claire ; Carless, Melanie ; Dyer, Thomas D. ; Curran, Joanne ; Charlesworth, Jac ; MacGregor, Stuart ; Nyholt, Dale ; Chasman, Daniel ; Ridker, Paul M. ; Schürks, Markus ; Blangero, John ; Griffiths, Lyn R. / A genome-wide analysis of 'Bounty' descendants implicates several novel variants in migraine susceptibility. In: Neurogenetics. 2012 ; Vol. 13, No. 3. pp. 261-266.
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