Concordance of genetic risk across migraine subgroups: Impact on current and future genetic association studies
Year: 2014
Type: article
Abstract: BACKGROUND: There has been intensive debate whether migraine with aura (MA) and migraine without aura (MO) should be considered distinct subtypes or part of the same disease spectrum. There is also discussion to what extent migraine cases collected in specialised headache clinics differ from cases from population cohorts, and how female cases differ from male cases with respect to their migraine. To assess the genetic overlap between these migraine subgroups, we examined genome-wide association (GWA) results from analysis of 23,285 migraine cases and 95,425 population-matched controls. METHODS: Detailed heterogeneity analysis of single-nucleotide polymorphism (SNP) effects (odds ratios) between migraine subgroups was performed for the 12 independent SNP loci significantly associated (p < 5 × 10(-8); thus surpassing the threshold for genome-wide significance) with migraine susceptibility. Overall genetic overlap was assessed using SNP effect concordance analysis (SECA) at over 23,000 independent SNPs. RESULTS: Significant heterogeneity of SNP effects (p het < 1.4 × 10(-3)) was observed between the MA and MO subgroups (for SNP rs9349379), and between the clinic- and population-based subgroups (for SNPs rs10915437, rs6790925 and rs6478241). However, for all 12 SNPs the risk-increasing allele was the same, and SECA found the majority of genome-wide SNP effects to be in the same direction across the subgroups. CONCLUSIONS: Any differences in common genetic risk across these subgroups are outweighed by the similarities. Meta-analysis of additional migraine GWA datasets, regardless of their major subgroup composition, will identify new susceptibility loci for migraine.
Source: Cephalalgia
Authors: Dale R Nyholt, Verneri Anttila, Bendik S Winsvold, Tobias Kurth, Hreinn Stefansson, Mikko Kallela, Rainer Malik, Boukje de Vries, Gisela M Terwindt, M Arfan Ikram, Anine H Stam, Lannie Ligthart, Tobias Freilinger, Michael Alexander, Bertram Muller-Myhsok, Stefan Schreiber, Thomas Meitinger, Arpo Aromaa, Johan G Eriksson, Jaakko Kaprio, Dorret I Boomsma, Cornelia van Duijn, Olli Raitakari, Marjo-Riitta Järvelin, John-Anker Zwart, Lydia Quaye, David P Strachan, Christian Kubisch, Michel D Ferrari, Arn M J M van den Maagdenberg, Martin Dichgans, Maija Wessman, George Davey Smith, Kari Stefansson, Daniel I Chasman, Aarno Palotie
Institutions: QIMR Berghofer Medical Research Institute, Broad Institute, Harvard University, Massachusetts General Hospital, Stanley Center for Psychiatric Research, Massachusetts Institute of Technology, Oslo University Hospital, University of Oslo, Brigham and Women's Hospital, Université de Bordeaux, Inserm, deCODE Genetics (Iceland), Helsinki University Hospital, LMU Klinikum, Institut für Schlaganfall- und Demenzforschung, Ludwig-Maximilians-Universität München, Leiden University Medical Center, Erasmus MC, Amsterdam Public Health, Vrije Universiteit Amsterdam, Amsterdam UMC Location Vrije Universiteit Amsterdam, University of Bonn, Munich Cluster for Systems Neurology, Max Planck Institute of Psychiatry, Christian-Albrechts-Universität zu Kiel, TUM Klinikum, Helmholtz Munich, Institut für Humangenetik, Technical University of Munich, Finnish Institute for Health and Welfare, University of Helsinki, Vaasa Central Hospital, Folkhälsans Forskningscentrum, Institute for Molecular Medicine Finland, University of Turku, Turku University Hospital, Oulu University Hospital, Imperial College London, University of Oulu, King's College London, University of London, St George's, University of London, Universität Ulm, University Medical Center Hamburg-Eppendorf, University of Bristol, MRC Integrative Epidemiology Unit, University of Iceland
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1581675459