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. 2002 Mar;70(3):652-62.
doi: 10.1086/339078. Epub 2002 Feb 8.

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

Maija Wessman  1 , Mikko Kallela, Mari A Kaunisto, Pia Marttila, Eric Sobel, Jaana Hartiala, Greg Oswell, Suzanne M Leal, Jeanette C Papp, Eija Hämäläinen, Petra Broas, Geoffrey Joslyn, Iiris Hovatta, Tero Hiekkalinna, Jaakko Kaprio, Jürg Ott, Rita M Cantor, John-Anker Zwart, Matti Ilmavirta, Hannele Havanka, Markus Färkkilä, Leena Peltonen, Aarno Palotie
Affiliations

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

Maija Wessman et al. Am J Hum Genet. 2002 Mar.

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.

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Figures

Figure 1
Figure 1
Two-point parametric linkage analyses (dominant model allowing for heterogeneity) for the 350-marker genomewide screen of 50 families with migraine. Blackened squares denote the two-point LOD scores when only individuals suffering from MA were considered to be affected; unblackened diamonds denote the two-point LOD scores for a broader phenotype, in which both individuals with MA and individuals with MO were considered to be affected. Analyses were performed by the LINKAGE program, as described in the text.
Figure 2
Figure 2
Multipoint parametric and nonparametric linkage analyses of 4q, with markers D4S2409 (96 cM), D4S2380 (101 cM), D4S1647 (105 cM), and D4S3240 (114 cM). Analyses were performed by the GENEHUNTER program, as described in the text. The vertical axis presents both the parametric (i.e., HLOD [unbroken line]) and nonparametric (i.e., NPLall [dotted line]) values along a 20-cM region of chromosome 4.
See this image and copyright information in PMC

References

Electronic Data-Base Information

    1. Center for Medical Genetics, Marshfield Medical Research Foundation, http://research.marshfieldclinic.org/genetics/ (for genetic-linkage distances)
    1. Fondation Jean Dausset CEPH, http://www.cephb.fr (for heterozygosity and allele sizes)
    1. Genome Database, The, http://www.gdb.org/ (for primers used for genotyping, heterozygosity, and allele sizes)
    1. Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim/ (for migraine [MIM 157300], FHM1 [MIM 141500], CACNA1A [MIM 601011], EA-2 [MIM 108500], SCA6 [MIM 183086], FHM2 [MIM 602481], typical familial migraine [MIM 300125], GC [MIM 139200], ENDRA [MIM 131243], ET-1 [MIM 131240], INSR [MIM 147670], GJB1 [MIM 304040], and Chargot-Marie-Tooth disease [MIM 302800])
    1. UCSC Human Genome Project Working Draft, http://genome.ucsc.edu/ (for gene information)

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