Heritability and genome-wide linkage analysis of migraine in the genetic isolate of Norfolk Island

Cox, Hannah C., Lea, Rod A., Bellis, Claire, Nyholt, Dale R., Dyer, Thomas D., Haupt, Larisa M., Charlesworth, Jac, Matovinovic, Elizabeth, Blangero, John, & Griffiths, Lyn R. (2012) Heritability and genome-wide linkage analysis of migraine in the genetic isolate of Norfolk Island. Gene, 494(1), pp. 119-123.

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Migraine is a common neurovascular disorder with a complex envirogenomic aetiology. In an effort to identify migraine susceptibility genes, we conducted a study of the isolated population of Norfolk Island, Australia. A large portion of the permanent inhabitants of Norfolk Island are descended from 18th Century English sailors involved in the infamous mutiny on the Bounty and their Polynesian consorts.

In total, 600 subjects were recruited including a large pedigree of 377 individuals with lineage to the founders. All individuals were phenotyped for migraine using International Classification of Headache Disorders-II criterion. All subjects were genotyped for a genome-wide panel of microsatellite markers. Genotype and phenotype data for the pedigree were analysed using heritability and linkage methods implemented in the programme SOLAR. Follow-up association analysis was performed using the CLUMP programme.

A total of 154 migraine cases (25%) were identified indicating the Norfolk Island population is high-risk for migraine. Heritability estimation of the 377-member pedigree indicated a significant genetic component for migraine (h2 = 0.53, P = 0.016). Linkage analysis showed peaks on chromosome 13q33.1 (P = 0.003) and chromosome 9q22.32 (P = 0.008). Association analysis of the key microsatellites in the remaining 223 unrelated Norfolk Island individuals showed evidence of association, which strengthen support for the linkage findings (P ≤ 0.05).

In conclusion, a genome-wide linkage analysis and follow-up association analysis of migraine in the genetic isolate of Norfolk Island provided evidence for migraine susceptibility loci on chromosomes 9q22.22 and 13q33.1.

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12 citations in Web of Science®
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ID Code: 62500
Item Type: Journal Article
Refereed: Yes
Keywords: Norfolk Island, Migraine, Genome Wide Linkage Analysis, Association, Chromosome 13, Chromosome 9
DOI: 10.1016/j.gene.2011.11.056
ISSN: 0378-1119
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > GENETICS (060400)
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2012 Elsevier
Deposited On: 13 Sep 2013 02:15
Last Modified: 20 May 2015 00:07

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