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

Lannie Ligthart (1) , Boukje de Vries (1) , Albert V Smith (1) , Mohammad Arfan Ikram (1) , Najaf Amin (1) , Jouke Jan Hottenga (1) , Stephany Koelewijn (1) , Mathijs Kattenberg (1) , Marleen H.M. de Moor (1) , Cecile (acjw) Janssens (1) , Yurii Sergeevich Aulchenko (1) , Ben A. Oostra (1) , Jcn de Geus (1) , Johannes Smit (1) , Frans Zitman (1) , A.G. Uitterlinden (1) , Albert Hofman (1) , Gonneke Willemsen (1) , Dale Nyholt (1) , Grant W Montgomery (1) , Gisela M Terwindt (1) , Vilmundur Gudnason (1) , Brenda Penninx (1) , Monique Breteler (1) , Michel Ferrari (1) , Leonore Launer (1) , Cornelia M. van Duijn (1) , Arn van den Maagdenberg (1) , Dorret I Boomsma (1)

1 Medstar Research Institute

Migraine is a common neurologic 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 x 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 MTDH gene, previously identified in the first clinic-based 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.

Mots clés: migraine; genome-wide association; meta-analysis

Lannie Ligthart, Boukje de Vries, Albert V Smith, Mohammad Arfan Ikram, Najaf Amin, et al.. Meta-analysis of genome-wide association for migraine in six population-based European cohorts. European Journal of Human Genetics, 2011, ⟨10.1038/ejhg.2011.48⟩. ⟨hal-00625926⟩