Genetic association studies of the chromosome 15 GABA-A receptor cluster in migraine with aura

Authors

  • Christian Netzer,

    1. Institute of Human Genetics, University of Cologne, Cologne, Germany
    2. Institute for Genetics, University of Cologne, Cologne, Germany
    3. Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
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  • Jan Freudenberg,

    1. Laboratories of Neurogenetics, Department of Neurology, UCSF, San Francisco
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  • Mohammad R. Toliat,

    1. Institute for Genetics, University of Cologne, Cologne, Germany
    2. Cologne Center for Genomics, University of Cologne, Cologne, Germany
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  • Axel Heinze,

    1. Kiel Pain and Headache Centre, Kiel, Germany
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  • Katja Heinze-Kuhn,

    1. Kiel Pain and Headache Centre, Kiel, Germany
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  • Holger Thiele,

    1. Institute for Genetics, University of Cologne, Cologne, Germany
    2. Cologne Center for Genomics, University of Cologne, Cologne, Germany
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  • Ingrid Goebel,

    1. Institute of Human Genetics, University of Cologne, Cologne, Germany
    2. Institute for Genetics, University of Cologne, Cologne, Germany
    3. Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
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  • Peter Nürnberg,

    1. Institute for Genetics, University of Cologne, Cologne, Germany
    2. Cologne Center for Genomics, University of Cologne, Cologne, Germany
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  • Louis J. Ptáček,

    1. Laboratories of Neurogenetics, Department of Neurology, UCSF, San Francisco
    2. Howard Hughes Medical Foundation, San Francisco
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  • Hartmut Göbel,

    1. Kiel Pain and Headache Centre, Kiel, Germany
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  • Unda Todt,

    1. Institute of Human Genetics, University of Cologne, Cologne, Germany
    2. Institute for Genetics, University of Cologne, Cologne, Germany
    3. Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
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  • Christian Kubisch

    Corresponding author
    1. Institute of Human Genetics, University of Cologne, Cologne, Germany
    2. Institute for Genetics, University of Cologne, Cologne, Germany
    3. Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
    4. Cologne Center for Genomics, University of Cologne, Cologne, Germany
    • Institute of Human Genetics, University of Cologne, Kerpener Strasse 34, 50931 Cologne, Germany.
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  • Please cite this article as follows: Netzer C, Freudenberg J, Toliat MR, Heinze A, Heinze-Kuhn K, Thiele H, Goebel I, Nürnberg P, Ptáček LJ, Göbel H, Todt U, Kubisch C. 2007. Genetic Association Studies of the Chromosome 15 GABA-A Receptor Cluster in Migraine With Aura. Am J Med Genet Part B 147B:37–41.

Abstract

Recently, a novel susceptibility locus for migraine with aura (MA) on chromosome 15q containing three GABA-A receptor subunits has been identified by linkage analysis in several large pedigrees. To further study the role of this locus in MA etiology we genotyped 56 SNPs capturing the known common haplotype variations of these three candidate genes in a sample comprising 270 MA patients and 273 matched controls. In a single marker analysis, four SNPs displayed nominally significant (P < 0.05) association with MA. However, after permutation-based correction for the number of tests performed, the P-values of these SNPs were non-significant. Furthermore, a replication study of two of these SNPs in a second independent sample of 379 MA patients and 379 controls did not result in a significant finding. We also compared haplotype estimates based on case–control genotypes. Again we could not demonstrate a significant association with the phenotype after correction for multiple testing. In summary, we found no convincing evidence for an involvement of common SNPs at the GABA-A receptor cluster on 15q11-q12 in the pathophysiology of MA. © 2007 Wiley-Liss, Inc.

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