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
22294494
TITLE
Confirmation that Xq27 and Xq28 are susceptibility loci for migraine in independent pedigrees and a case-control cohort.
ABSTRACT
Investigations into migraine genetics have suggested that susceptibility loci exist on the X chromosome. These reports are supported by evidence that demonstrates male probands as having a higher proportion of affected first-degree relatives as well as the female preponderance of 3:1 that the disorder displays. We have previously implicated the Xq24-28 locus in migraine using two independent multigenerational Australian pedigrees that demonstrated excess allele sharing at the Xq24, Xq27 and Xq28 loci. Here, we expand this work to investigate a further six independent migraine pedigrees using 11 microsatellite markers spanning the Xq27–28 region. Furthermore, 11 candidate genes are investigated in an Australian case-control cohort consisting of 500 cases and 500 controls. Microsatellite analysis showed evidence of excess allele sharing to the Xq27 marker DXS8043 (LOD* 1.38 P00.005) in MF879 whilst a second independent pedigree showed excess allele sharing to DXS8061 at Xq28 (LOD* 1.5 P00.004). Furthermore, analysis of these key markers in a case control cohort showed significant association to migraine in females at the DXS8043 marker (T1 P00.009) and association with MO at DXS8061 (T1 P00.05). Further analysis of 11 key genes across these regions showed significant association of a three-marker risk haplotype in the NSDHL gene at Xq28 (P00.0082). The results of this study add further support to the presence of migraine susceptibility loci on chromosome Xq27 and Xq28 as well as point to potential candidate genes in the regions that warrant further investigation.
DATE PUBLISHED
2012 Feb
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2011/08/24
accepted 2011/12/19
aheadofprint 2012/02/01
entrez 2012/02/02 06:00
pubmed 2012/02/02 06:00
medline 2012/05/23 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Maher BH Maher B H BH Genomics Research Centre, School of Medical Science, Griffith Health Institute, Griffith University, Gold Coast, Queensland 4222, Australia.
Kerr M Kerr M M
Cox HC Cox H C HC
MacMillan JC MacMillan J C JC
Brimage PJ Brimage P J PJ
Esposito T Esposito T T
Gianfrancesco F Gianfrancesco F F
Haupt LM Haupt L M LM
Nyholt DR Nyholt D R DR
Lea RA Lea R A RA
Griffiths LR Griffiths L R LR
INVESTIGATORS
JOURNAL
VOLUME: 13
ISSUE: 1
TITLE: Neurogenetics
ISOABBREVIATION: Neurogenetics
YEAR: 2012
MONTH: Feb
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1364-6753
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Neurogenetics
COUNTRY: United States
ISSNLINKING: 1364-6745
NLMUNIQUEID: 9709714
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
GRANTS
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Australia
Case-Control Studies
Chromosomes, Human, X genetics
Female genetics
Genetic Predisposition to Disease genetics
Genotype genetics
Haplotypes genetics
Humans genetics
Male genetics
Microsatellite Repeats genetics
Migraine Disorders genetics
Pedigree genetics
Polymorphism, Single Nucleotide genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's