Consistently replicating locus linked to migraine on 10q22-q23

Anttila, Verneri, Nyholt, Dale R., Kallela, Mikko, Artto, Ville, Vepsalainen, Salli, Jakkula, Eveliina, Wennerstrom, Annika, Tikka-Kleemola, Paeivi, Kaunisto, Mari A., Hamalainen, Eija, Widen, Elisabeth, Terwilliger, Joseph, Merikangas, Kathleen, Montgomery, Grant W., Martin, Nicholas G., Daly, Mark, Kaprio, Jaakko, Peltonen, Leena, Farkkila, Markus, Wessman, Maija and Palotie, Aarno (2008) Consistently replicating locus linked to migraine on 10q22-q23. American Journal of Human Genetics, 82 5: 1051-1063. doi:10.1016/j.ajhg.2008.03.003


Author Anttila, Verneri
Nyholt, Dale R.
Kallela, Mikko
Artto, Ville
Vepsalainen, Salli
Jakkula, Eveliina
Wennerstrom, Annika
Tikka-Kleemola, Paeivi
Kaunisto, Mari A.
Hamalainen, Eija
Widen, Elisabeth
Terwilliger, Joseph
Merikangas, Kathleen
Montgomery, Grant W.
Martin, Nicholas G.
Daly, Mark
Kaprio, Jaakko
Peltonen, Leena
Farkkila, Markus
Wessman, Maija
Palotie, Aarno
Title Consistently replicating locus linked to migraine on 10q22-q23
Journal name American Journal of Human Genetics   Check publisher's open access policy
ISSN 0002-9297
1537-6605
Publication date 2008-05-09
Year available 2008
Sub-type Article (original research)
DOI 10.1016/j.ajhg.2008.03.003
Open Access Status Not yet assessed
Volume 82
Issue 5
Start page 1051
End page 1063
Total pages 13
Place of publication Cambridge, MA, United States
Publisher Cell Press
Language eng
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.
Keyword Genetics & Heredity
Genetics & Heredity
GENETICS & HEREDITY
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID U54 RR020278
AA013320
R01 NS037675
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
 
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