title: A susceptibility locus for migraine with aura, on chromosome 4q24.
abstract: Migraine is a complex neurovascular disorder with substantial evidence supporting a genetic contribution. Prior attempts to localize susceptibility loci for common forms of migraine have not produced conclusive evidence of linkage or association. To date, no genomewide screen for migraine has been published. We report results from a genomewide screen of 50 multigenerational, clinically well-defined Finnish families showing intergenerational transmission of migraine with aura (MA). The families were screened using 350 polymorphic microsatellite markers, with an average intermarker distance of 11 cM. Significant evidence of linkage was found between the MA phenotype and marker D4S1647 on 4q24. Using parametric two-point linkage analysis and assuming a dominant mode of inheritance, we found for this marker a maximum LOD score of 4.20 under locus homogeneity (P=.000006) or locus heterogeneity (P=.000011). Multipoint parametric (HLOD = 4.45; P=.0000058) and nonparametric (NPL(all) = 3.43; P=.0007) analyses support linkage in this region. Statistically significant linkage was not observed in any other chromosomal region.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles 90095-7088, USA.
authors.forename: Maija
authors.initials: M
authors.lastname: Wessman
authors.forename: Mikko
authors.initials: M
authors.lastname: Kallela
authors.forename: Mari A
authors.initials: MA
authors.lastname: Kaunisto
authors.forename: Pia
authors.initials: P
authors.lastname: Marttila
authors.forename: Eric
authors.initials: E
authors.lastname: Sobel
authors.forename: Jaana
authors.initials: J
authors.lastname: Hartiala
authors.forename: Greg
authors.initials: G
authors.lastname: Oswell
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Leal
authors.forename: Jeanette C
authors.initials: JC
authors.lastname: Papp
authors.forename: Eija
authors.initials: E
authors.lastname: Hämäläinen
authors.forename: Petra
authors.initials: P
authors.lastname: Broas
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Joslyn
authors.forename: Iiris
authors.initials: I
authors.lastname: Hovatta
authors.forename: Tero
authors.initials: T
authors.lastname: Hiekkalinna
authors.forename: Jaakko
authors.initials: J
authors.lastname: Kaprio
authors.forename: Jürg
authors.initials: J
authors.lastname: Ott
authors.forename: Rita M
authors.initials: RM
authors.lastname: Cantor
authors.forename: John-Anker
authors.initials: JA
authors.lastname: Zwart
authors.forename: Matti
authors.initials: M
authors.lastname: Ilmavirta
authors.forename: Hannele
authors.initials: H
authors.lastname: Havanka
authors.forename: Markus
authors.initials: M
authors.lastname: Färkkilä
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: Aarno
authors.initials: A
authors.lastname: Palotie
mesh_terms: D002874:Chromosome Mapping; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D005387:Finland; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D008126:Lod Score; D018895:Microsatellite Repeats / Q000235:genetics; D020325:Migraine with Aura / Q000235:genetics*; D010641:Phenotype; D018709:Statistics, Nonparametric