Meta-analysis of genome-wide association for migraine in six population-based European cohorts.
Ligthart L., de Vries B., Smith AV., Ikram MA., Amin N., Hottenga J-J., Koelewijn SC., Kattenberg VM., de Moor MHM., Janssens ACJW., Aulchenko YS., Oostra BA., de Geus EJC., Smit JH., Zitman FG., Uitterlinden AG., Hofman A., Willemsen G., Nyholt DR., Montgomery GW., Terwindt GM., Gudnason V., Penninx BWJH., Breteler M., Ferrari MD., Launer LJ., van Duijn CM., van den Maagdenberg AMJM., Boomsma DI.
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.