QIMR Genetic Epidemiology Laboratory Home Page

Genetic Epidemiology, Translational Neurogenomics,
Psychiatric Genetics and Statistical Genetics
Publications

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.
QIMR Home Page
GenEpi Home Page
About GenEpi
Publications
Contacts
Research
Staff Index
Collaborators
Software Tools
Computing Resources
Studies
Search
GenEpi Intranet

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