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
16773568
TITLE
Trait components provide tools to dissect the genetic susceptibility of migraine.
ABSTRACT
The commonly used "end diagnosis" phenotype that is adopted in linkage and association studies of complex traits is likely to represent an oversimplified model of the genetic background of a disease. This is also likely to be the case for common types of migraine, for which no convincingly associated genetic variants have been reported. In headache disorders, most genetic studies have used end diagnoses of the International Headache Society (IHS) classification as phenotypes. Here, we introduce an alternative strategy; we use trait components--individual clinical symptoms of migraine--to determine affection status in genomewide linkage analyses of migraine-affected families. We identified linkage between several traits and markers on chromosome 4q24 (highest LOD score under locus heterogeneity [HLOD] 4.52), a locus we previously reported to be linked to the end diagnosis migraine with aura. The pulsation trait identified a novel locus on 17p13 (HLOD 4.65). Additionally, a trait combination phenotype (IHS full criteria) revealed a locus on 18q12 (HLOD 3.29), and the age at onset trait revealed a locus on 4q28 (HLOD 2.99). Furthermore, suggestive or nearly suggestive evidence of linkage to four additional loci was observed with the traits phonophobia (10q22) and aggravation by physical exercise (12q21, 15q14, and Xp21), and, interestingly, these loci have been linked to migraine in previous studies. Our findings suggest that the use of symptom components of migraine instead of the end diagnosis provides a useful tool in stratifying the sample for genetic studies.
DATE PUBLISHED
2006 Jul
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2005/12/09
accepted 2006/03/31
aheadofprint 2006/05/10
pubmed 2006/06/15 09:00
medline 2006/08/15 09:00
entrez 2006/06/15 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Anttila V Anttila V V Finnish Genome Center, Helsinki, Finland.
Kallela M Kallela M M
Oswell G Oswell G G
Kaunisto MA Kaunisto M A MA
Nyholt DR Nyholt D R DR
Hamalainen E Hamalainen E E
Havanka H Havanka H H
Ilmavirta M Ilmavirta M M
Terwilliger J Terwilliger J J
Sobel E Sobel E E
Peltonen L Peltonen L L
Kaprio J Kaprio J J
Farkkila M Farkkila M M
Wessman M Wessman M M
Palotie A Palotie A A
INVESTIGATORS
JOURNAL
VOLUME: 79
ISSUE: 1
TITLE: American journal of human genetics
ISOABBREVIATION: Am. J. Hum. Genet.
YEAR: 2006
MONTH: Jul
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
Journal Article
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Chromosome Mapping
Female
Genetic Heterogeneity
Genetic Predisposition to Disease
Humans
Lod Score
Male
Migraine Disorders genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
PMC1474123 NLM
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