Dataset Information

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.

SUBMITTER: Wessman M

PROVIDER: S-EPMC384944 | biostudies-literature | 2002 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A susceptibility locus for migraine with aura, on chromosome 4q24.

Wessman Maija M 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

American journal of human genetics 20020208 3

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 w ...[more]

PMID: 11836652

Similar Datasets

Project description:It is unclear whether patients diagnosed according to International Classification of Headache Disorders criteria for migraine with aura (MA) and migraine without aura (MO) experience distinct disorders or whether their migraine subtypes are genetically related.Using a novel gene-based (statistical) approach, we aimed to identify individual genes and pathways associated both with MA and MO.Gene-based tests were performed using genome-wide association summary statistic results from the most recent International Headache Genetics Consortium study comparing 4505 MA cases with 34,813 controls and 4038 MO cases with 40,294 controls. After accounting for non-independence of gene-based test results, we examined the significance of the proportion of shared genes associated with MA and MO.We found a significant overlap in genes associated with MA and MO. Of the total 1514 genes with a nominally significant gene-based p value (pgene-based???0.05) in the MA subgroup, 107 also produced pgene-based???0.05 in the MO subgroup. The proportion of overlapping genes is almost double the empirically derived null expectation, producing significant evidence of gene-based overlap (pleiotropy) (pbinomial-test = 1.5?×?10(-4)). Combining results across MA and MO, six genes produced genome-wide significant gene-based p values. Four of these genes (TRPM8, UFL1, FHL5 and LRP1) were located in close proximity to previously reported genome-wide significant SNPs for migraine, while two genes, TARBP2 and NPFF separated by just 259?bp on chromosome 12q13.13, represent a novel risk locus. The genes overlapping in both migraine types were enriched for functions related to inflammation, the cardiovascular system and connective tissue.Our results provide novel insight into the likely genes and biological mechanisms that underlie both MA and MO, and when combined with previous data, highlight the neuropeptide FF-amide peptide encoding gene (NPFF) as a novel candidate risk gene for both types of migraine.

Dataset Information

A susceptibility locus for migraine with aura, on chromosome 4q24.

Publications

A susceptibility locus for migraine with aura, on chromosome 4q24.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets