Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
22197687
TITLE
Heritability and genome-wide linkage analysis of migraine in the genetic isolate of Norfolk Island.
ABSTRACT
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 (h(2)=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.
Copyright © 2011 Elsevier B.V. All rights reserved.
DATE PUBLISHED
2012 Feb 15
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2011/08/24
revised 2011/11/02
accepted 2011/11/22
aheadofprint 2011/12/14
entrez 2011/12/27 06:00
pubmed 2011/12/27 06:00
medline 2012/03/31 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Cox HC Cox Hannah C HC Genomics Research Centre, Griffith Health Institute, Gold Coast Campus, Griffith University, Queensland, Australia.
Lea RA Lea Rod A RA
Bellis C Bellis Claire C
Nyholt DR Nyholt Dale R DR
Dyer TD Dyer Thomas D TD
Haupt LM Haupt Larisa M LM
Charlesworth J Charlesworth Jac J
Matovinovic E Matovinovic Elizabeth E
Blangero J Blangero John J
Griffiths LR Griffiths Lyn R LR
INVESTIGATORS
JOURNAL
VOLUME: 494
ISSUE: 1
TITLE: Gene
ISOABBREVIATION: Gene
YEAR: 2012
MONTH: Feb
DAY: 15
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1879-0038
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Gene
COUNTRY: Netherlands
ISSNLINKING: 0378-1119
NLMUNIQUEID: 7706761
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Validation Studies
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
MH59490 NIMH NIH HHS United States
R37 MH059490 NIMH NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Australia
Female
Genetic Linkage
Genetic Predisposition to Disease
Genotype
Humans
Male
Middle Aged
Migraine Disorders genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
NIHMS401730 NLM
PMC3837682 NLM
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