Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
25179292
TITLE
Concordance of genetic risk across migraine subgroups: Impact on current and future genetic association studies.
ABSTRACT
BACKGROUND NlmCategory: 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 NlmCategory: 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 NlmCategory: 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 NlmCategory: 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.
© International Headache Society 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
DATE PUBLISHED
2015 May
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2014/07/18
accepted 2014/07/23
aheadofprint 2014/09/01
entrez 2014/09/03 06:00
pubmed 2014/09/03 06:00
medline 2016/01/14 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Nyholt DR Nyholt Dale R DR Neurogenetics Laboratory, QIMR Berghofer, Australia Dale.Nyholt@qimrberghofer.edu.au.
International Headache Genetics Consortium
Anttila V Anttila Verneri V Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, USA Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, USA Harvard Medical School, USA Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, USA.
Winsvold BS Winsvold Bendik S BS FORMI and Department of Neurology, Oslo University Hospital and University of Oslo, Norway.
Kurth T Kurth Tobias T Institut National de la Santé et de la Recherche Médicale (INSERM) Research Center for Epidemiology and Biostatistics (U897) - Team Neuroepidemiology, France University of Bordeaux, France Department of Medicine, Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, USA.
Stefansson H Stefansson Hreinn H deCODE Genetics, Iceland.
Kallela M Kallela Mikko M Department of Neurology, Helsinki University Central Hospital, Finland.
Malik R Malik Rainer R Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität, Germany.
Vries Bd Vries Boukje de Bd Department of Human Genetics, Leiden University Medical Centre, the Netherlands.
Terwindt GM Terwindt Gisela M GM Department of Neurology, Leiden University Medical Centre, the Netherlands.
Ikram MA Ikram M Arfan MA Department of Epidemiology, Erasmus University Medical Centre, the Netherlands Department of Radiology, Erasmus University Medical Centre, the Netherlands Department of Neurology, Erasmus University Medical Centre, the Netherlands.
Stam AH Stam Anine H AH Department of Neurology, Leiden University Medical Centre, the Netherlands.
Ligthart L Ligthart Lannie L Department of Biological Psychology, VU University, the Netherlands EMGO+ Institute for Health and Care Research, VU University Medical Centre, the Netherlands.
Freilinger T Freilinger Tobias T Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität, Germany Department of Neurology, Klinikum der Universität München, Germany.
Alexander M Alexander Michael M Department of Genomics, Life & Brain Center, University of Bonn, Germany Institute of Human Genetics, University of Bonn, Germany.
Muller-Myhsok B Muller-Myhsok Bertram B Max Planck Institute of Psychiatry, Germany Munich Cluster for Systems Neurology (SyNergy), Germany.
Schreiber S Schreiber Stefan S Institute of Clinical Molecular Biology, Christian Albrechts University, Germany Department of Internal Medicine I, Christian Albrechts University, Germany.
Meitinger T Meitinger Thomas T Institute of Human Genetics, Helmholtz Center Munich, Germany Institute of Human Genetics, Klinikum Rechts der Isar, Technische Universität München, Germany.
Aromaa A Aromaa Arpo A National Institute for Health and Welfare, Finland.
Eriksson JG Eriksson Johan G JG National Institute for Health and Welfare, Finland Institute of Genetics, Folkhälsan Research Center, Finland Department of General Practice, Helsinki University Central Hospital, Helsinki, Finland Vaasa Central Hospital, Finland Department of General Practice and Primary Health Care, University of Helsinki, Finland.
Kaprio J Kaprio Jaakko J Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland Department of Public Health, Hjelt Institute, University of Helsinki, Finland Department of Mental Health and Alcohol Research, National Institute for Health and Welfare, Finland.
Boomsma DI Boomsma Dorret I DI Department of Biological Psychology, VU University, the Netherlands.
Duijn Cv Duijn Cornelia van Cv Department of Epidemiology, Erasmus University Medical Centre, the Netherlands.
Raitakari O Raitakari Olli O Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku University Hospital, Finland Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Finland.
Järvelin MR Järvelin Marjo-Riitta MR Institute of Health Sciences, University of Oulu, Finland Unit of Primary Care, Oulu University Hospital, Finland Department of Children, Young People and Families, National Institute for Health and Welfare, Finland Department of Epidemiology and Biostatistics, School of Public Health, MRC-Health Protection Agency (HPA) Centre for Environment and Health, Faculty of Medicine, Imperial College, UK Biocenter Oulu, University of Oulu, Finland.
Zwart JA Zwart John-Anker JA FORMI and Department of Neurology, Oslo University Hospital and University of Oslo, Norway.
Quaye L Quaye Lydia L Department of Twin Research and Genetic Epidemiology, King's College London, UK.
Strachan DP Strachan David P DP Division of Population Health Sciences and Education, St George's, University of London, UK.
Kubisch C Kubisch Christian C Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Germany Institute of Human Genetics, University of Ulm, Germany.
Ferrari MD Ferrari Michel D MD Department of Neurology, Leiden University Medical Centre, the Netherlands.
van den Maagdenberg AM van den Maagdenberg Arn M J M AM Department of Human Genetics, Leiden University Medical Centre, the Netherlands Department of Neurology, Leiden University Medical Centre, the Netherlands.
Dichgans M Dichgans Martin M Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität, Germany Munich Cluster for Systems Neurology (SyNergy), Germany.
Wessman M Wessman Maija M Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, USA Institute of Genetics, Folkhälsan Research Center, Finland.
Smith GD Smith George Davey GD Medical Research Council Integrative Epidemiology Unit (IEU) at the University of Bristol, School of Social and Community Medicine, UK.
Stefansson K Stefansson Kari K deCODE Genetics, Iceland School of Medicine, University of Iceland, Iceland.
Chasman DI Chasman Daniel I DI Department of Medicine, Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, USA.
Palotie A Palotie Aarno A Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, USA Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, USA Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, USA Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland Psychiatric & Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, USA Department of Neurology, Massachusetts General Hospital, USA.
INVESTIGATORS
JOURNAL
VOLUME: 35
ISSUE: 6
TITLE: Cephalalgia : an international journal of headache
ISOABBREVIATION: Cephalalgia
YEAR: 2015
MONTH: May
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1468-2982
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Cephalalgia
COUNTRY: England
ISSNLINKING: 0333-1024
NLMUNIQUEID: 8200710
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
MC_UU_12013/1 Medical Research Council United Kingdom
GENERAL NOTE
KEYWORDS
KEYWORD
Migraine
association
genetic
genome-wide
heterogeneity
subgroups
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Female
Genetic Association Studies
Genetic Predisposition to Disease
Humans
Male
Migraine Disorders genetics
Polymorphism, Single Nucleotide genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's