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; CARDIoGRAM Consortium and the International Headache Genetics Consortium

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 WillenborgHong-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, CARDIoGRAM Consortium and the International Headache Genetics Consortium

Research output: Contribution to journal › Article (Academic Journal) › peer-review

57 Citations (Scopus)

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
Publication status	Published - Jun 2015

Access to Document

10.1212/NXG.0000000000000010

Handle.net

Persistent link

MRC UoB UNITE Unit - Programme 1
Davey Smith, G. (Principal Investigator)
1/06/13 → 31/03/18
Project: Research

Cite this

Winsvold, B. S., Nelson, C. P., Malik, R., Gormley, P., Anttila, V., Vander Heiden, J., 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., ... CARDIoGRAM Consortium and the International Headache Genetics Consortium (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{bab18ab9c550429f8467d4fc0828c2ed,

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 {Vander Heiden}, Jason 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 Hong-Hee Won and Jes Olesen and Ville Artto and Assimes, {Themistocles L} and Stefan Blankenberg and Boomsma, {Dorret I} and Lynn Cherkas and {Davey Smith}, George and Epstein, {Stephen E} and Jeanette Erdmann and Ferrari, {Michel D} and Hartmut G{\"o}bel and Hall, {Alistair S} and Marjo-Riitta Jarvelin 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 {CARDIoGRAM Consortium and the International Headache Genetics Consortium}",

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, Vander Heiden, J, 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, H-H, Olesen, J, Artto, V, Assimes, TL, Blankenberg, S, Boomsma, DI, Cherkas, L, Davey Smith, G, Epstein, SE, Erdmann, J, Ferrari, MD, Göbel, H, Hall, AS, Jarvelin, M-R, 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 & CARDIoGRAM Consortium and the International Headache Genetics Consortium 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 - Vander Heiden, Jason

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 - Davey Smith, George

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 - CARDIoGRAM Consortium and the International Headache Genetics Consortium

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.

U2 - 10.1212/NXG.0000000000000010

DO - 10.1212/NXG.0000000000000010

M3 - Article (Academic Journal)

C2 - 27066539

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

Access to Document

Handle.net

Fingerprint

Projects

MRC UoB UNITE Unit - Programme 1

Cite this