Genetic analysis for a shared biological basis between migraine and coronary artery disease

Bendik S. Winsvold; Christopher P. Nelson; Rainer Malik; Padhraig Gormley; Verneri Anttila; Jason Vander Heiden; Katherine S. Elliott; Line M. Jacobsen; Priit Palta; Najaf Amin; Boukje De Vries; Eija Hämäläinen; Tobias Freilinger; M. Arfan Ikram; Thorsten Kessler; Markku Koiranen; Lannie Ligthart; George McMahon; Linda M. Pedersen; Christina Willenborg; Hong Hee Won; Jes Olesen; Ville Artto; Themistocles L. Assimes; Stefan Blankenberg; Dorret I. Boomsma; Lynn Cherkas; George Davey Smith; Stephen E. Epstein; Jeanette Erdmann; Michel D. Ferrari; Hartmut Göbel; Alistair S. Hall; Marjo Riitta Jarvelin; Mikko Kallela; Jaakko Kaprio; Sekar Kathiresan; Terho Lehtimäki; Ruth McPherson; Winfried März; Dale R. Nyholt; Christopher J. O'Donnell; Lydia Quaye; Daniel J. Rader; Olli Raitakari; Robert Roberts; Heribert Schunkert; Markus Schürks; Alexandre F.R. Stewart; Gisela M. Terwindt; Unnur Thorsteinsdottir; Arn M.J.M. Van Den Maagdenberg; Cornelia Van Duijn; Maija Wessman; Tobias Kurth; Christian Kubisch; Martin Dichgans; Daniel I. Chasman; Chris Cotsapas; John Anker Zwart; Nilesh J. Samani; Aarno Palotie

doi:10.1212/NXG.0000000000000010

Genetic analysis for a shared biological basis between migraine and coronary artery disease

Bendik S. Winsvold
, Christopher P. Nelson
, Rainer Malik
, Padhraig Gormley
, Verneri Anttila
, Jason Vander Heiden
, Katherine S. Elliott
, Line M. Jacobsen
, Priit Palta
, Najaf Amin
, Boukje De Vries
, Eija Hämäläinen
, Tobias Freilinger
, M. Arfan Ikram
, Thorsten Kessler
, Markku Koiranen
, Lannie Ligthart
, George McMahon
, Linda M. Pedersen
, Christina Willenborg

Hong Hee Won, Jes Olesen, Ville Artto, Themistocles L. Assimes, Stefan Blankenberg, Dorret I. Boomsma, Lynn Cherkas, George Davey Smith, Stephen E. Epstein, Jeanette Erdmann, Michel D. Ferrari, Hartmut Göbel, Alistair S. Hall, Marjo Riitta Jarvelin, Mikko Kallela, Jaakko Kaprio, Sekar Kathiresan, Terho Lehtimäki, Ruth McPherson, Winfried März, Dale R. Nyholt, Christopher J. O'Donnell, Lydia Quaye, Daniel J. Rader, Olli Raitakari, Robert Roberts, Heribert Schunkert, Markus Schürks, Alexandre F.R. Stewart, Gisela M. Terwindt, Unnur Thorsteinsdottir, Arn M.J.M. Van Den Maagdenberg, Cornelia Van Duijn, Maija Wessman, Tobias Kurth, Christian Kubisch, Martin Dichgans, Daniel I. Chasman, Chris Cotsapas, John Anker Zwart, Nilesh J. Samani, Aarno Palotie

University of Oslo
Wellcome Trust
University Hospitals of Leicester NHS Trust
University of Leicester
Ludwig Maximilian University of Munich
Munich Cluster for Systems Neurology (SyNergy)
Broad Institute
Psychiatric and Neurodevelopmental Genetics Unit
Analytic and Translational Genetics Unit
Brigham and Women’s Hospital
Yale University
University of Oxford
University of Helsinki
Erasmus University Rotterdam
Leiden University
University of Tübingen
Technical University of Munich
German Centre for Cardiovascular Research
University of Oulu
VU University Medical Center
Medical Research Council
University of Lübeck
Center for Human Genetic Research
Massachusetts General Hospital
University of Copenhagen
Helsinki University Hospital
Stanford University
Johannes Gutenberg University Mainz
King's College London
University of Bristol
Washington Hospital Center
Kiel Pain and Headache Center
University of Leeds
National Institute for Health and Welfare
Imperial College London
Fimlab Laboratories
Tampere University
University of Ottawa
SYNLAB International GmbH
Medical University of Graz
Heidelberg University
Queensland University of Technology
Boston University's Framingham Heart Study
University of Pennsylvania
University of Turku
University of Duisburg-Essen
deCODE genetics
University of Iceland
Folkhalsan
Harvard University
Institut national de la santé et de la recherche médicale
Université de Bordeaux
University of Hamburg

Research output: Contribution to journal › Article › peer-review

62 Scopus citations

Abstract

Objective: To apply genetic analysis of genome-wide association data to study the extent and nature of a shared biological basis between migraine and coronary artery disease (CAD). Methods: Four separate methods for cross-phenotype genetic analysis were applied on data from 2 large-scale genome-wide association studies of migraine (19,981 cases, 56,667 controls) and CAD (21,076 cases, 63,014 controls). The first 2 methods quantified the extent of overlapping risk variants and assessed the load of CAD risk loci in migraineurs. Genomic regions of shared risk were then identified by analysis of covariance patterns between the 2 phenotypes and by querying known genome-wide significant loci. Results: We found a significant overlap of genetic risk loci for migraine and CAD. When stratified by migraine subtype, this was limited to migraine without aura, and the overlap was protective in that patients with migraine had a lower load of CAD risk alleles than controls. Genes indicated by 16 shared risk loci point to mechanisms with potential roles in migraine pathogenesis and CAD, including endothelial dysfunction (PHACTR1) and insulin homeostasis (GIP). Conclusions: The results suggest that shared biological processes contribute to risk of migraine and CAD, but surprisingly this commonality is restricted to migraine without aura and the impact is in opposite directions. Understanding the mechanisms underlying these processes and their opposite relationship to migraine and CAD may improve our understanding of both disorders.

Original language	English
Pages (from-to)	e10
Journal	Neurology: Genetics
Volume	1
Issue number	1
DOIs	https://doi.org/10.1212/NXG.0000000000000010
State	Published - Jun 2015
Externally published	Yes

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SDG 3 Good Health and Well-being

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10.1212/NXG.0000000000000010

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Winsvold, B. S., Nelson, C. P., Malik, R., Gormley, P., Anttila, V., Heiden, J. V., Elliott, K. S., Jacobsen, L. M., Palta, P., Amin, N., De Vries, B., Hämäläinen, E., Freilinger, T., Ikram, M. A., Kessler, T., Koiranen, M., Ligthart, L., McMahon, G., Pedersen, L. M., ... Palotie, A. (2015). Genetic analysis for a shared biological basis between migraine and coronary artery disease. Neurology: Genetics, 1(1), e10. https://doi.org/10.1212/NXG.0000000000000010

@article{0982a60c9b25429e8045287c204c4bf0,

title = "Genetic analysis for a shared biological basis between migraine and coronary artery disease",

abstract = "Objective: To apply genetic analysis of genome-wide association data to study the extent and nature of a shared biological basis between migraine and coronary artery disease (CAD). Methods: Four separate methods for cross-phenotype genetic analysis were applied on data from 2 large-scale genome-wide association studies of migraine (19,981 cases, 56,667 controls) and CAD (21,076 cases, 63,014 controls). The first 2 methods quantified the extent of overlapping risk variants and assessed the load of CAD risk loci in migraineurs. Genomic regions of shared risk were then identified by analysis of covariance patterns between the 2 phenotypes and by querying known genome-wide significant loci. Results: We found a significant overlap of genetic risk loci for migraine and CAD. When stratified by migraine subtype, this was limited to migraine without aura, and the overlap was protective in that patients with migraine had a lower load of CAD risk alleles than controls. Genes indicated by 16 shared risk loci point to mechanisms with potential roles in migraine pathogenesis and CAD, including endothelial dysfunction (PHACTR1) and insulin homeostasis (GIP). Conclusions: The results suggest that shared biological processes contribute to risk of migraine and CAD, but surprisingly this commonality is restricted to migraine without aura and the impact is in opposite directions. Understanding the mechanisms underlying these processes and their opposite relationship to migraine and CAD may improve our understanding of both disorders.",

author = "Winsvold, \{Bendik S.\} and Nelson, \{Christopher P.\} and Rainer Malik and Padhraig Gormley and Verneri Anttila and Heiden, \{Jason Vander\} and Elliott, \{Katherine S.\} and Jacobsen, \{Line M.\} and Priit Palta and Najaf Amin and \{De Vries\}, Boukje and Eija H{\"a}m{\"a}l{\"a}inen and Tobias Freilinger and Ikram, \{M. Arfan\} and Thorsten Kessler and Markku Koiranen and Lannie Ligthart and George McMahon and Pedersen, \{Linda M.\} and Christina Willenborg and Won, \{Hong Hee\} and Jes Olesen and Ville Artto and Assimes, \{Themistocles L.\} and Stefan Blankenberg and Boomsma, \{Dorret I.\} and Lynn Cherkas and Smith, \{George Davey\} and Epstein, \{Stephen E.\} and Jeanette Erdmann and Ferrari, \{Michel D.\} and Hartmut G{\"o}bel and Hall, \{Alistair S.\} and Jarvelin, \{Marjo Riitta\} and Mikko Kallela and Jaakko Kaprio and Sekar Kathiresan and Terho Lehtim{\"a}ki and Ruth McPherson and Winfried M{\"a}rz and Nyholt, \{Dale R.\} and O'Donnell, \{Christopher J.\} and Lydia Quaye and Rader, \{Daniel J.\} and Olli Raitakari and Robert Roberts and Heribert Schunkert and Markus Sch{\"u}rks and Stewart, \{Alexandre F.R.\} and Terwindt, \{Gisela M.\} and Unnur Thorsteinsdottir and \{Van Den Maagdenberg\}, \{Arn M.J.M.\} and \{Van Duijn\}, Cornelia and Maija Wessman and Tobias Kurth and Christian Kubisch and Martin Dichgans and Chasman, \{Daniel I.\} and Chris Cotsapas and Zwart, \{John Anker\} and Samani, \{Nilesh J.\} and Aarno Palotie",

note = "Publisher Copyright: {\textcopyright} 2015 American Academy of Neurology.",

year = "2015",

month = jun,

doi = "10.1212/NXG.0000000000000010",

language = "English",

volume = "1",

pages = "e10",

journal = "Neurology: Genetics",

issn = "2376-7839",

publisher = "Lippincott Williams and Wilkins",

number = "1",

}

Winsvold, BS, Nelson, CP, Malik, R, Gormley, P, Anttila, V, Heiden, JV, Elliott, KS, Jacobsen, LM, Palta, P, Amin, N, De Vries, B, Hämäläinen, E, Freilinger, T, Ikram, MA, Kessler, T, Koiranen, M, Ligthart, L, McMahon, G, Pedersen, LM, Willenborg, C, Won, HH, Olesen, J, Artto, V, Assimes, TL, Blankenberg, S, Boomsma, DI, Cherkas, L, Smith, GD, Epstein, SE, Erdmann, J, Ferrari, MD, Göbel, H, Hall, AS, Jarvelin, MR, Kallela, M, Kaprio, J, Kathiresan, S, Lehtimäki, T, McPherson, R, März, W, Nyholt, DR, O'Donnell, CJ, Quaye, L, Rader, DJ, Raitakari, O, Roberts, R, Schunkert, H, Schürks, M, Stewart, AFR, Terwindt, GM, Thorsteinsdottir, U, Van Den Maagdenberg, AMJM, Van Duijn, C, Wessman, M, Kurth, T, Kubisch, C, Dichgans, M, Chasman, DI, Cotsapas, C, Zwart, JA, Samani, NJ & Palotie, A 2015, 'Genetic analysis for a shared biological basis between migraine and coronary artery disease', Neurology: Genetics, vol. 1, no. 1, pp. e10. https://doi.org/10.1212/NXG.0000000000000010

TY - JOUR

T1 - Genetic analysis for a shared biological basis between migraine and coronary artery disease

AU - Winsvold, Bendik S.

AU - Nelson, Christopher P.

AU - Malik, Rainer

AU - Gormley, Padhraig

AU - Anttila, Verneri

AU - Heiden, Jason Vander

AU - Elliott, Katherine S.

AU - Jacobsen, Line M.

AU - Palta, Priit

AU - Amin, Najaf

AU - De Vries, Boukje

AU - Hämäläinen, Eija

AU - Freilinger, Tobias

AU - Ikram, M. Arfan

AU - Kessler, Thorsten

AU - Koiranen, Markku

AU - Ligthart, Lannie

AU - McMahon, George

AU - Pedersen, Linda M.

AU - Willenborg, Christina

AU - Won, Hong Hee

AU - Olesen, Jes

AU - Artto, Ville

AU - Assimes, Themistocles L.

AU - Blankenberg, Stefan

AU - Boomsma, Dorret I.

AU - Cherkas, Lynn

AU - Smith, George Davey

AU - Epstein, Stephen E.

AU - Erdmann, Jeanette

AU - Ferrari, Michel D.

AU - Göbel, Hartmut

AU - Hall, Alistair S.

AU - Jarvelin, Marjo Riitta

AU - Kallela, Mikko

AU - Kaprio, Jaakko

AU - Kathiresan, Sekar

AU - Lehtimäki, Terho

AU - McPherson, Ruth

AU - März, Winfried

AU - Nyholt, Dale R.

AU - O'Donnell, Christopher J.

AU - Quaye, Lydia

AU - Rader, Daniel J.

AU - Raitakari, Olli

AU - Roberts, Robert

AU - Schunkert, Heribert

AU - Schürks, Markus

AU - Stewart, Alexandre F.R.

AU - Terwindt, Gisela M.

AU - Thorsteinsdottir, Unnur

AU - Van Den Maagdenberg, Arn M.J.M.

AU - Van Duijn, Cornelia

AU - Wessman, Maija

AU - Kurth, Tobias

AU - Kubisch, Christian

AU - Dichgans, Martin

AU - Chasman, Daniel I.

AU - Cotsapas, Chris

AU - Zwart, John Anker

AU - Samani, Nilesh J.

AU - Palotie, Aarno

PY - 2015/6

Y1 - 2015/6

N2 - Objective: To apply genetic analysis of genome-wide association data to study the extent and nature of a shared biological basis between migraine and coronary artery disease (CAD). Methods: Four separate methods for cross-phenotype genetic analysis were applied on data from 2 large-scale genome-wide association studies of migraine (19,981 cases, 56,667 controls) and CAD (21,076 cases, 63,014 controls). The first 2 methods quantified the extent of overlapping risk variants and assessed the load of CAD risk loci in migraineurs. Genomic regions of shared risk were then identified by analysis of covariance patterns between the 2 phenotypes and by querying known genome-wide significant loci. Results: We found a significant overlap of genetic risk loci for migraine and CAD. When stratified by migraine subtype, this was limited to migraine without aura, and the overlap was protective in that patients with migraine had a lower load of CAD risk alleles than controls. Genes indicated by 16 shared risk loci point to mechanisms with potential roles in migraine pathogenesis and CAD, including endothelial dysfunction (PHACTR1) and insulin homeostasis (GIP). Conclusions: The results suggest that shared biological processes contribute to risk of migraine and CAD, but surprisingly this commonality is restricted to migraine without aura and the impact is in opposite directions. Understanding the mechanisms underlying these processes and their opposite relationship to migraine and CAD may improve our understanding of both disorders.

AB - Objective: To apply genetic analysis of genome-wide association data to study the extent and nature of a shared biological basis between migraine and coronary artery disease (CAD). Methods: Four separate methods for cross-phenotype genetic analysis were applied on data from 2 large-scale genome-wide association studies of migraine (19,981 cases, 56,667 controls) and CAD (21,076 cases, 63,014 controls). The first 2 methods quantified the extent of overlapping risk variants and assessed the load of CAD risk loci in migraineurs. Genomic regions of shared risk were then identified by analysis of covariance patterns between the 2 phenotypes and by querying known genome-wide significant loci. Results: We found a significant overlap of genetic risk loci for migraine and CAD. When stratified by migraine subtype, this was limited to migraine without aura, and the overlap was protective in that patients with migraine had a lower load of CAD risk alleles than controls. Genes indicated by 16 shared risk loci point to mechanisms with potential roles in migraine pathogenesis and CAD, including endothelial dysfunction (PHACTR1) and insulin homeostasis (GIP). Conclusions: The results suggest that shared biological processes contribute to risk of migraine and CAD, but surprisingly this commonality is restricted to migraine without aura and the impact is in opposite directions. Understanding the mechanisms underlying these processes and their opposite relationship to migraine and CAD may improve our understanding of both disorders.

UR - https://www.scopus.com/pages/publications/84962516331

U2 - 10.1212/NXG.0000000000000010

DO - 10.1212/NXG.0000000000000010

M3 - Article

AN - SCOPUS:84962516331

SN - 2376-7839

VL - 1

SP - e10

JO - Neurology: Genetics

JF - Neurology: Genetics

IS - 1

ER -

Genetic analysis for a shared biological basis between migraine and coronary artery disease

Abstract

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