TY - JOUR
T1 - Meta-analysis of genome-wide association for migraine in six population-based European cohorts
AU - Ligthart, Lannie
AU - De Vries, Boukje
AU - Smith, Albert V.
AU - Ikram, M. Arfan
AU - Amin, Najaf
AU - Hottenga, Jouke Jan
AU - Koelewijn, Stephany C.
AU - Kattenberg, V. Mathijs
AU - De Moor, Marleen H.M.
AU - Janssens, A. Cecile J.W.
AU - Aulchenko, Yurii S.
AU - Oostra, Ben A.
AU - De Geus, Eco J.C.
AU - Smit, Johannes H.
AU - Zitman, Frans G.
AU - Uitterlinden, André G.
AU - Hofman, Albert
AU - Willemsen, Gonneke
AU - Nyholt, Dale R.
AU - Montgomery, Grant W.
AU - Terwindt, Gisela M.
AU - Gudnason, Vilmundur
AU - Penninx, Brenda W.J.H.
AU - Breteler, Monique
AU - Ferrari, Michel D.
AU - Launer, Lenore J.
AU - Van Duijn, Cornelia M.
AU - Van Den Maagdenberg, Arn M.J.M.
AU - Boomsma, Dorret I.
PY - 2011/8
Y1 - 2011/8
N2 - 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-value10 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-value0.026). This finding is consistent with the involvement of the glutamate pathway in migraine. Additional research is necessary to further confirm the involvement of glutamate.
AB - 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-value10 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-value0.026). This finding is consistent with the involvement of the glutamate pathway in migraine. Additional research is necessary to further confirm the involvement of glutamate.
UR - https://www.scopus.com/pages/publications/79960628620
U2 - 10.1038/ejhg.2011.48
DO - 10.1038/ejhg.2011.48
M3 - Article
C2 - 21448238
AN - SCOPUS:79960628620
SN - 1018-4813
VL - 19
SP - 901
EP - 907
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 8
ER -