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Meta-Analysis
. 2011 Aug;19(8):901-7.
doi: 10.1038/ejhg.2011.48. Epub 2011 Mar 30.

Meta-analysis of genome-wide association for migraine in six population-based European cohorts

Lannie Ligthart  1 , Boukje de Vries, Albert V Smith, M Arfan Ikram, Najaf Amin, Jouke-Jan Hottenga, Stephany C Koelewijn, V Mathijs Kattenberg, Marleen H M de Moor, A Cecile J W Janssens, Yurii S Aulchenko, Ben A Oostra, Eco J C de Geus, Johannes H Smit, Frans G Zitman, André G Uitterlinden, Albert Hofman, Gonneke Willemsen, Dale R Nyholt, Grant W Montgomery, Gisela M Terwindt, Vilmundur Gudnason, Brenda W J H Penninx, Monique Breteler, Michel D Ferrari, Lenore J Launer, Cornelia M van Duijn, Arn M J M van den Maagdenberg, Dorret I Boomsma
Affiliations
Meta-Analysis

Meta-analysis of genome-wide association for migraine in six population-based European cohorts

Lannie Ligthart et al. Eur J Hum Genet. 2011 Aug.

Abstract

Migraine is a common neurological disorder with a genetically complex background. This paper describes a meta-analysis of genome-wide association (GWA) studies on migraine, performed by the Dutch-Icelandic migraine genetics (DICE) consortium, which brings together six population-based European migraine cohorts with a total sample size of 10,980 individuals (2446 cases and 8534 controls). A total of 32 SNPs showed marginal evidence for association at a P-value<10(-5). The best result was obtained for SNP rs9908234, which had a P-value of 8.00 × 10(-8). This top SNP is located in the nerve growth factor receptor (NGFR) gene. However, this SNP did not replicate in three cohorts from the Netherlands and Australia. Of the other 31 SNPs, 18 SNPs were tested in two replication cohorts, but none replicated. In addition, we explored previously identified candidate genes in the meta-analysis data set. This revealed a modest gene-based significant association between migraine and the metadherin (MTDH) gene, previously identified in the first clinic-based GWA study (GWAS) for migraine (Bonferroni-corrected gene-based P-value=0.026). This finding is consistent with the involvement of the glutamate pathway in migraine. Additional research is necessary to further confirm the involvement of glutamate.

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Figures

Figure 1
Figure 1
Q–Q plot showing the expected and observed distribution of P-values in the meta-analysis that included the five Dutch samples and the Icelandic sample. The genomic inflation factor (λ) for the meta-analysis was 1.022.
Figure 2
Figure 2
Manhattan plot showing the P-values by chromosome for the meta-analysis.
See this image and copyright information in PMC

References

    1. Headache classification subcommittee of the International Headache Society The International Classification of Headache Disorders2nd edn. Cephalalgia; 2004. Vol 24 (Suppl 1), pp9–160. - PubMed
    1. Russell MB, Rasmussen BK, Fenger K, Olesen J. Migraine without aura and migraine with aura are distinct clinical entities: a study of four hundred and eighty-four male and female migraineurs from the general population. Cephalalgia. 1996;16:239–245. - PubMed
    1. Russell MB, Ulrich V, Gervil M, Olesen J. Migraine without aura and migraine with aura are distinct disorders. A population-based twin survey. Headache. 2002;42:332–336. - PubMed
    1. Kallela M, Wessman M, Havanka H, Palotie A, Farkkila M. Familial migraine with and without aura: clinical characteristics and co-occurrence. Eur J Neurol. 2001;8:441–449. - PubMed
    1. Ligthart L, Boomsma DI, Martin NG, Stubbe JH, Nyholt DR. Migraine with aura and migraine without aura are not distinct entities: further evidence from a large Dutch population study. Twin Res Hum Genet. 2006;9:54–63. - PubMed

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