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
18423523
TITLE
Consistently replicating locus linked to migraine on 10q22-q23.
ABSTRACT
Here, we present the results of two genome-wide scans in two diverse populations in which a consistent use of recently introduced migraine-phenotyping methods detects and replicates a locus on 10q22-q23, with an additional independent replication. No genetic variants have been convincingly established in migraine, and although several loci have been reported, none of them has been consistently replicated. We employed the three known migraine-phenotyping methods (clinical end diagnosis, latent-class analysis, and trait-component analysis) with robust multiple testing correction in a large sample set of 1675 individuals from 210 migraine families from Finland and Australia. Genome-wide multipoint linkage analysis that used the Kong and Cox exponential model in Finns detected a locus on 10q22-q23 with highly significant evidence of linkage (LOD 7.68 at 103 cM in female-specific analysis). The Australian sample showed a LOD score of 3.50 at the same locus (100 cM), as did the independent Finnish replication study (LOD score 2.41, at 102 cM). In addition, four previously reported loci on 8q21, 14q21, 18q12, and Xp21 were also replicated. A shared-segment analysis of 10q22-q23 linked Finnish families identified a 1.6-9.5 cM segment, centered on 101 cM, which shows in-family homology in 95% of affected Finns. This region was further studied with 1323 SNPs. Although no significant association was observed, four regions warranting follow-up studies were identified. These results support the use of symptomology-based phenotyping in migraine and suggest that the 10q22-q23 locus probably contains one or more migraine susceptibility variants.
DATE PUBLISHED
2008 May
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2007/11/28
revised 2008/02/04
accepted 2008/03/03
pubmed 2008/04/22 09:00
medline 2008/07/17 09:00
entrez 2008/04/22 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Anttila V Anttila Verneri V Biomedicum Helsinki, Research Program in Molecular Medicine, University of Helsinki, 00290 Helsinki, Finland.
Nyholt DR Nyholt Dale R DR
Kallela M Kallela Mikko M
Artto V Artto Ville V
Vepsäläinen S Vepsäläinen Salli S
Jakkula E Jakkula Eveliina E
Wennerström A Wennerström Annika A
Tikka-Kleemola P Tikka-Kleemola Päivi P
Kaunisto MA Kaunisto Mari A MA
Hämäläinen E Hämäläinen Eija E
Widén E Widén Elisabeth E
Terwilliger J Terwilliger Joseph J
Merikangas K Merikangas Kathleen K
Montgomery GW Montgomery Grant W GW
Martin NG Martin Nicholas G NG
Daly M Daly Mark M
Kaprio J Kaprio Jaakko J
Peltonen L Peltonen Leena L
Färkkilä M Färkkilä Markus M
Wessman M Wessman Maija M
Palotie A Palotie Aarno A
INVESTIGATORS
JOURNAL
VOLUME: 82
ISSUE: 5
TITLE: American journal of human genetics
ISOABBREVIATION: Am. J. Hum. Genet.
YEAR: 2008
MONTH: May
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1537-6605
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Am J Hum Genet
COUNTRY: United States
ISSNLINKING: 0002-9297
NLMUNIQUEID: 0370475
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
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
R01 NS37675 NINDS NIH HHS United States
U54 RR020278 NCRR NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Australia
Chromosome Mapping
Chromosomes, Human, Pair 10 genetics
Female genetics
Finland genetics
Genetic Predisposition to Disease genetics
Humans genetics
Lod Score genetics
Male genetics
Migraine Disorders genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
PMC2427232 NLM
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