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.
authors.affiliation: Biomedicum Helsinki, Research Program in Molecular Medicine, University of Helsinki, 00290 Helsinki, Finland.
authors.forename: Verneri
authors.initials: V
authors.lastname: Anttila
authors.forename: Dale R
authors.initials: DR
authors.lastname: Nyholt
authors.forename: Mikko
authors.initials: M
authors.lastname: Kallela
authors.forename: Ville
authors.initials: V
authors.lastname: Artto
authors.forename: Salli
authors.initials: S
authors.lastname: Vepsäläinen
authors.forename: Eveliina
authors.initials: E
authors.lastname: Jakkula
authors.forename: Annika
authors.initials: A
authors.lastname: Wennerström
authors.forename: Päivi
authors.initials: P
authors.lastname: Tikka-Kleemola
authors.forename: Mari A
authors.initials: MA
authors.lastname: Kaunisto
authors.forename: Eija
authors.initials: E
authors.lastname: Hämäläinen
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Widén
authors.forename: Joseph
authors.initials: J
authors.lastname: Terwilliger
authors.forename: Kathleen
authors.initials: K
authors.lastname: Merikangas
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.forename: Mark
authors.initials: M
authors.lastname: Daly
authors.forename: Jaakko
authors.initials: J
authors.lastname: Kaprio
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: Markus
authors.initials: M
authors.lastname: Färkkilä
authors.forename: Maija
authors.initials: M
authors.lastname: Wessman
authors.forename: Aarno
authors.initials: A
authors.lastname: Palotie
mesh_terms: D001315:Australia; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D005260:Female; D005387:Finland; D020022:Genetic Predisposition to Disease; D006801:Humans; D008126:Lod Score; D008297:Male; D008881:Migraine Disorders / Q000235:genetics*