Genetic Epidemiology, Psychiatric Genetics, Asthma 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
16080125
TITLE
Genomewide significant linkage to migrainous headache on chromosome 5q21.
ABSTRACT
Familial typical migraine is a common, complex disorder that shows strong familial aggregation. Using latent-class analysis (LCA), we identified subgroups of people with migraine/severe headache in a community sample of 12,245 Australian twins (60% female), drawn from two cohorts of individuals aged 23-90 years who completed an interview based on International Headache Society criteria. We report results from genomewide linkage analyses involving 756 twin families containing a total of 790 independent sib pairs (130 affected concordant, 324 discordant, and 336 unaffected concordant for LCA-derived migraine). Quantitative-trait linkage analysis produced evidence of significant linkage on chromosome 5q21 and suggestive linkage on chromosomes 8, 10, and 13. In addition, we replicated previously reported typical-migraine susceptibility loci on chromosomes 6p12.2-p21.1 and 1q21-q23, the latter being within 3 cM of the rare autosomal dominant familial hemiplegic migraine gene (ATP1A2), a finding which potentially implicates ATP1A2 in familial typical migraine for the first time. Linkage analyses of individual migraine symptoms for our six most interesting chromosomes provide tantalizing hints of the phenotypic and genetic complexity of migraine. Specifically, the chromosome 1 locus is most associated with phonophobia; the chromosome 5 peak is predominantly associated with pulsating headache; the chromosome 6 locus is associated with activity-prohibiting headache and photophobia; the chromosome 8 locus is associated with nausea/vomiting and moderate/severe headache; the chromosome 10 peak is most associated with phonophobia and photophobia; and the chromosome 13 peak is completely due to association with photophobia. These results will prove to be invaluable in the design and analysis of future linkage and linkage disequilibrium studies of migraine.
DATE PUBLISHED
2005 Sep
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2005/05/10
accepted 2005/06/29
aheadofprint 2005/07/28
pubmed 2005/08/05 09:00
medline 2006/02/07 09:00
entrez 2005/08/05 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Nyholt DR Nyholt Dale R DR Queensland Institute of Medical Research, Brisbane, Australia. daleN@qimr.edu.au
Morley KI Morley Katherine I KI
Ferreira MA Ferreira Manuel A R MA
Medland SE Medland Sarah E SE
Boomsma DI Boomsma Dorret I DI
Heath AC Heath Andrew C AC
Merikangas KR Merikangas Kathleen R KR
Montgomery GW Montgomery Grant W GW
Martin NG Martin Nicholas G NG
INVESTIGATORS
JOURNAL
VOLUME: 77
ISSUE: 3
TITLE: American journal of human genetics
ISOABBREVIATION: Am. J. Hum. Genet.
YEAR: 2005
MONTH: Sep
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Print
ISSN: 0002-9297
ISSNTYPE: Print
MEDLINE JOURNAL
MEDLINETA: Am J Hum Genet
COUNTRY: United States
ISSNLINKING: 0002-9297
NLMUNIQUEID: 0370475
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
AA007535 NIAAA NIH HHS United States
AA013320 NIAAA NIH HHS United States
AA013326 NIAAA NIH HHS United States
AA014041 NIAAA NIH HHS United States
AA07728 NIAAA NIH HHS United States
AA10249 NIAAA NIH HHS United States
AA11998 NIAAA NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Aged
Aged, 80 and over
Chromosomes, Human, Pair 5 genetics
Cohort Studies genetics
Female genetics
Genetic Linkage genetics
Genetic Predisposition to Disease genetics
Genome, Human genetics
Humans genetics
Interviews as Topic genetics
Male genetics
Middle Aged genetics
Migraine Disorders physiopathology
Photophobia genetics
Sodium-Potassium-Exchanging ATPase genetics
Twin Studies as Topic genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
EC 3.6.1.- ATP1A2 protein, human
EC 3.6.3.9 Sodium-Potassium-Exchanging ATPase
OTHER ID's
OTHERID SOURCE
PMC1226215 NLM