Localization of a Gene for Migraine without Aura to Chromosome 4q21

Abstract

Migraine is a common form of headache and has a significant genetic component. Here, we report linkage results from a study in Iceland of migraine without aura (MO). The study group comprised patients with migraine recruited by neurologists and from the registry of the Icelandic Migraine Society, as well as through the use of a questionnaire sent to a random sample of 20,000 Icelanders. Migraine diagnoses were made and confirmed using diagnostic criteria established by the International Headache Society. A genome-wide scan with multipoint allele-sharing methods was performed on 289 patients suffering from MO. Linkage was observed to a locus on chromosome 4q21 (LOD=2.05; P=.001). The locus reported here overlaps a locus (MGR1) reported elsewhere for patients with migraine with aura (MA) in the Finnish population. This replication of the MGR1 locus in families with MO indicates that the gene we have mapped may contribute to both MA and MO. Further analysis indicates that the linkage evidence improves for affected females and, especially, with a slightly relaxed definition of MO (LOD=4.08; P=7.2 x 10(-6)).

Migraine genetics and prospects for pharmacotherapy

“…Several loci have been identified in genomewide scans, the first in Finnish families with MA, implicated 4q24 [Wessman et al, 2002]. A nearby region, 4q21, was implicated in 103 Icelandic families with MO [Bjornsson et al, 2003]. In a Swedish family with MA and MO there was significant linkage to 6p12.2-21.1, although mutation screening in potential susceptibility loci under this linkage peak showed negative results [Carlsson et al, 2002].…”

The use of pedigree, sib-pair and association studies of common diseases for genetic mapping and epidemiology

“…In the past few years it became feasible to genotype cheaply large pedigrees with much greater numbers of microsatellites than were previously used for genome scans, and statistical programs that are now available permit efficient computation of linkage even in complex pedigrees 28,29 . These advances allowed a substantial increase in the scale of pedigree-based linkage studies 2,4,[30][31][32][33][34][35][36][37][38] . Inadequate technology and statistical methodology have similarly hindered implementation of alternatives to pedigreebased mapping.…”

“…Most of deCODE's studies have involved genotyping several hundred affected individuals, using >1,000 markers. Although each study has yielded interesting results, leading to fine-mapping and gene-identification efforts, several have failed to achieve clear statistical significance 2,5,37,38 . deCODE's experiences suggest two avenues for extended pedigree designs.…”

Mapping for dyslexia and related cognitive trait loci provides strong evidence for further risk genes on chromosome 6p21

“…The genotyping was performed at DeCode Genetics (Reykjavik, Iceland) according to procedures described elsewhere [Bjornsson et al, 2003]. All genotyped markers were checked for Mendelian incompatibilities using PEDCHECK v. 1.1 [O'Connell and Weeks, 1998] and were discarded in case of incompatibilities.…”