Genetic Epidemiology, Psychiatric Genetics, Asthma 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
26660531
TITLE
Gene-based pleiotropy across migraine with aura and migraine without aura patient groups.
ABSTRACT
INTRODUCTION NlmCategory: BACKGROUND
H.Z. and E.E. contributed equally to this work. A.M.J.M.v.d.M. and D.R.N. jointly directed this work.It is unclear whether patients diagnosed according to International Classification of Headache Disorders criteria for migraine with aura (MA) and migraine without aura (MO) experience distinct disorders or whether their migraine subtypes are genetically related.
AIM NlmCategory: OBJECTIVE
Using a novel gene-based (statistical) approach, we aimed to identify individual genes and pathways associated both with MA and MO.
METHODS NlmCategory: METHODS
Gene-based tests were performed using genome-wide association summary statistic results from the most recent International Headache Genetics Consortium study comparing 4505 MA cases with 34,813 controls and 4038 MO cases with 40,294 controls. After accounting for non-independence of gene-based test results, we examined the significance of the proportion of shared genes associated with MA and MO.
RESULTS NlmCategory: RESULTS
We found a significant overlap in genes associated with MA and MO. Of the total 1514 genes with a nominally significant gene-based p value (pgene-based ≤ 0.05) in the MA subgroup, 107 also produced pgene-based ≤ 0.05 in the MO subgroup. The proportion of overlapping genes is almost double the empirically derived null expectation, producing significant evidence of gene-based overlap (pleiotropy) (pbinomial-test = 1.5 × 10(-4)). Combining results across MA and MO, six genes produced genome-wide significant gene-based p values. Four of these genes (TRPM8, UFL1, FHL5 and LRP1) were located in close proximity to previously reported genome-wide significant SNPs for migraine, while two genes, TARBP2 and NPFF separated by just 259 bp on chromosome 12q13.13, represent a novel risk locus. The genes overlapping in both migraine types were enriched for functions related to inflammation, the cardiovascular system and connective tissue.
CONCLUSIONS NlmCategory: CONCLUSIONS
Our results provide novel insight into the likely genes and biological mechanisms that underlie both MA and MO, and when combined with previous data, highlight the neuropeptide FF-amide peptide encoding gene (NPFF) as a novel candidate risk gene for both types of migraine.
International Headache Society 2015.
DATE PUBLISHED
2015 Dec 8
HISTORY
PUBSTATUS PUBSTATUSDATE
entrez 2015/12/15 06:00
pubmed 2015/12/15 06:00
medline 2015/12/15 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Zhao H Zhao Huiying H Institute of Health and Biomedical Innovation, Queensland University of Technology, Australia QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Eising E Eising Else E Department of Human Genetics, Leiden University Medical Centre, The Netherlands.
de Vries B de Vries Boukje B Department of Human Genetics, Leiden University Medical Centre, The Netherlands.
Vijfhuizen LS Vijfhuizen Lisanne S LS Department of Human Genetics, Leiden University Medical Centre, The Netherlands.
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.
Stam AH Stam Anine H AH 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.
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 and Epileptology and Hertie-Institute for Clinical Brain Research, University of Tuebingen, Germany.
Alexander M Alexander Michael M Department of Genomics, Life & Brain Center, University of Bonn, Germany Institute of Human Genetics, University of Bonn, Germany.
Müller-Myhsok B Müller-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.
Aromas A Aromas 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, Finland Vaasa Central Hospital, Finland Department of General Practice and Primary Health Care, University of Helsinki, Finland.
Boomsma DI Boomsma Dorret I DI Department of Biological Psychology, VU University, The Netherlands.
van Duijn CM van Duijn Cornelia M CM Department of Epidemiology, Erasmus University Medical Centre, The Netherlands.
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.
Kubisch C Kubisch Christian C Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Germany.
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.
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.
Martin NG Martin Nicholas G NG QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Montgomery GW Montgomery Grant W GW QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Ferrari MD Ferrari Michel D MD Department of Neurology, Leiden University Medical Centre, The Netherlands.
Terwindt GM Terwindt Gisela M GM 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.
Nyholt DR Nyholt Dale R DR Institute of Health and Biomedical Innovation, Queensland University of Technology, Australia QIMR Berghofer Medical Research Institute, Brisbane, Australia d.nyholt@qut.edu.au.
INVESTIGATORS
JOURNAL
VOLUME:
ISSUE:
TITLE: Cephalalgia : an international journal of headache
ISOABBREVIATION: Cephalalgia
YEAR: 2015
MONTH: Dec
DAY: 8
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
COMMENTS AND CORRECTIONS
GRANTS
GENERAL NOTE
KEYWORDS
KEYWORD
Migraine
association
aura
gene-based
genome-wide
pleiotropy
MESH HEADINGS
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's