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

Citation

Cox, HC and Lea, RA and Bellis, C and Carless, M and Dyer, TD and Curran, J and Charlesworth, J and Macgregor, S and Nyholt, D and Chasman, D and Ridker, PM and Schurks, M and Blangero, J and Griffiths, LR, A genome-wide analysis of 'Bounty' descendants implicates several novel variants in migraine susceptibility, Neurogenetics, 13, (3) pp. 261-266. ISSN 1364-6753 (2012) [Refereed Article]


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Copyright Statement

Copyright 2012 Springer-Verlag

DOI: doi:10.1007/s10048-012-0325-x

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 (h2 = 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.

Item Details

Item Type:Refereed Article
Keywords:migraine, association, gene, Norfolk Island, zinc finger protein
Research Division:Biological Sciences
Research Group:Genetics
Research Field:Neurogenetics
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Inherited Diseases (incl. Gene Therapy)
Author:Charlesworth, J (Dr Jac Charlesworth)
ID Code:78792
Year Published:2012
Web of Science® Times Cited:15
Deposited By:Menzies Institute for Medical Research
Deposited On:2012-07-26
Last Modified:2013-05-27
Downloads:1 View Download Statistics

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