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.
N1 - Funding Information: The Age, Gene/Environment Susceptibility Reykjavik Study is funded by NIH contract N01-AG-12100, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association) and the Althingi (the Icelandic Parliament). The Erasmus Rucphen Family was supported by grants from The Netherlands Organization for Scientific Research (NWO), Erasmus MC and the Netherlands Genomics Initiative (NGI)-sponsored Center of Medical Systems Biology (CMSB). The genotyping for the ERF study was supported by EUROSPAN (European Special Populations Research Network) through the European Commission FP6 STRP grant (018947; LSHG-CT-2006-01947). The ERF study was further supported by grants from the Netherlands Organisation for Scientific Research (NWO) (903-52-291, M.D.F., Vici 918.56.602, M.D.F, 907-00-217 G.M.T.), Erasmus MC, the Centre for Medical Systems Biology (CMSB1 and CMSB2), and the Netherlands Genomics Initiative (NGI). We are grateful to all patients and their relatives, general practitioners and neurologists for their contributions and to P Veraart for her help in genealogy, Jeannette Vergeer for the supervision of the laboratory work and P Snijders for his help in data collection. For NESDA and NTR, funding was obtained from the Netherlands Organization for Scientific Research (NWO: MagW/ZonMW): Genetic basis of anxiety and depression (904-61-090); Genetics of individual differences in smoking initiation and persistence (NWO 985-10-002); Resolving cause and effect in the association between exercise and well-being (904-61-193); Twin family database for behavior genomics studies (480-04-004); Twin research focusing on behavior (400-05-717); Genetic determinants of risk behavior in relation to alcohol use and alcohol use disorder (Addiction-31160008); Genotype/phenotype database for behavior genetic and genetic epidemiological studies (40-0056-98-9032); Spinozapremie (SPI 56-464-14192); CMSB: Center for Medical Systems Biology (NWO Genomics); NBIC/ BioAssist/RK/2008.024); BBMRI –NL: Biobanking and Biomolecular Resources Research Infrastructure (184.021.007); the VU University: Institute for Health and Care Research (EMGO+ ) and Neuroscience Campus Amsterdam (NCA); the European Science Foundation (ESF): Genomewide analyses of European twin and population cohorts (EU/QLRT-2001-01254); European Community’s Seventh Framework Program (FP7/2007-2013): ENGAGE (HEALTH-F4-2007-201413); the European Science Council (ERC) Genetics of Mental Illness (230374); Rutgers University Cell and DNA Repository cooperative agreement (NIMH U24 MH068457-06); Collaborative study of the genetics of DZ twinning (NIH R01D0042157-01A); the Genetic Association Information Network, a public–private partnership between the NIH and Pfizer Inc., Affymetrix Inc. and Abbott Laboratories. The infrastructure for the NESDA study (http://www.nesda.nl) is funded through the Geestkracht program of the Netherlands Organization for Health Research and Development (ZonMw, Grant number 10-000-1002) and is supported by participating universities and mental health care organizations (VU University Medical Center, GGZ inGeest, Arkin, Leiden University Medical Center, GGZ Rivierduinen, University Medical Center Groningen, Lentis, GGZ Friesland, GGZ Drenthe, Scientific Institute for Quality of Health Care (IQ Healthcare), Netherlands Institute for Health Services Research (NIVEL) and Netherlands Institute of Mental Health and Addiction (Trimbos)). SNP genotyping was funded by the Genetic Association Information Network (GAIN) of the Foundation for the US National Institutes of Health (NTR1/NESDA) and the Spinozapremie (NWO/SPI 56-464-14192; NTR2). Statistical analyses were partly carried out on the Genetic Cluster Computer (NWO 480-05-003). The Rotterdam Study (I, I, and II) are funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), the Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA) and the Municipality of Rotterdam. The generation and management of GWAS genotype data for the Rotterdam Study is supported by the Netherlands Organization of Scientific Research NWO Investments (nr. 175.010.2005.011, 911-03-012). The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE and RIDE2), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), the Municipality of Rotterdam and the Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO) project nr. 050-060-810. We thank Pascal Arp, Mila Jhamai, Dr Michael Moorhouse, Marijn Verkerk and Sander Bervoets for their help in creating the GWAS database. We are grateful to the study participants, the staff from the Rotterdam Study and the participating general practioners and pharmacists. For the Australian cohort, we thank the Australian National Health and Medical Research Council (NHMRC; Grants 241944, 339462, 389927, 389875, 389891, 389892, 389938, 443036, 442915, 442981, 496739, 552485 and 552498) and the Australian Research Council (A7960034, A79906588, A79801419, DP0212016 and DP0343921) for funding. GWM and DRN are supported by the NHMRC Fellowship and the Australian Research Council Future Fellowship Schemes. We thank N Martin, P Visscher, D Duffy, A Henders, B Usher, E Souzeau, A Kuot, A McMellon, MJ Wright, MJ Campbell, A Caracella, L Bowdler, S Smith, S Gordon, B Haddon, D Smyth, H Beeby, O Zheng and B Chapman for their input into project management, databases, phenotype collection, and sample collection, processing and genotyping.
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
SN - 1018-4813
VL - 19
SP - 901
EP - 907
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 8
ER -