A susceptibility locus for migraine with aura, on chromosome 4q24.
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.
Wessman
Maija
M
Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles 90095-7088, USA.
Kallela
Mikko
M
Kaunisto
Mari A
MA
Marttila
Pia
P
Sobel
Eric
E
Hartiala
Jaana
J
Oswell
Greg
G
Leal
Suzanne M
SM
Papp
Jeanette C
JC
Hämäläinen
Eija
E
Broas
Petra
P
Joslyn
Geoffrey
G
Hovatta
Iiris
I
Hiekkalinna
Tero
T
Kaprio
Jaakko
J
Ott
Jürg
J
Cantor
Rita M
RM
Zwart
John-Anker
JA
Ilmavirta
Matti
M
Havanka
Hannele
H
Färkkilä
Markus
M
Peltonen
Leena
L
Palotie
Aarno
A
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