Shared genetic risk between migraine and coronary artery disease: A genome-wide analysis of common variants
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Shared genetic risk between migraine and coronary artery disease : A genome-wide analysis of common variants. / Winsvold, Bendik S.; Bettella, Francesco; Witoelar, Aree; Anttila, Verneri; Gormley, Padhraig; Kurth, Tobias; Terwindt, Gisela M.; Freilinger, Tobias; Frei, Oleksander; Shadrin, Alexey; Wang, Yunpeng; Dale, Anders M.; van den Maagdenberg, Arn M.J.M.; Nyholt, Dale R.; Palotie, Aarno; Andreassen, Ole A.; Zwart, John Anker; Artto, Ville; Belin, Andrea Carmine; Boomsma, Dorret I.; Børte, Sigrid; Chasman, Daniel I.; Cherkas, Lynn; Christensen, Anne Francke; Cormand, Bru; Cuenca-Leon, Ester; Davey-Smith, George; Dichgans, Martin; van Duijn, Cornelia; Eising, Else; Esko, Tonu; Esserlind, Ann Louise; Ferrari, Michel; Frants, Rune R.; Freilinger, Tobias; Furlotte, Nick; Griffiths, Lyn; Hamalainen, Eija; Hansen, Thomas Folkmann; Hiekkala, Marjo; Arfan Ikram, M.; Ingason, Andres; Järvelin, Marjo Riitta; Kajanne, Risto; Kallela, Mikko; Kaprio, Jaakko; Kaunisto, Mari; Kubisch, Christian; Kurki, Mitja; Olesen, Jes; International Headache Genetics Consortium.
I: PLoS ONE, Bind 12, Nr. 9, e0185663, 2017.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Shared genetic risk between migraine and coronary artery disease
T2 - A genome-wide analysis of common variants
AU - Winsvold, Bendik S.
AU - Bettella, Francesco
AU - Witoelar, Aree
AU - Anttila, Verneri
AU - Gormley, Padhraig
AU - Kurth, Tobias
AU - Terwindt, Gisela M.
AU - Freilinger, Tobias
AU - Frei, Oleksander
AU - Shadrin, Alexey
AU - Wang, Yunpeng
AU - Dale, Anders M.
AU - van den Maagdenberg, Arn M.J.M.
AU - Nyholt, Dale R.
AU - Palotie, Aarno
AU - Andreassen, Ole A.
AU - Zwart, John Anker
AU - Artto, Ville
AU - Belin, Andrea Carmine
AU - Boomsma, Dorret I.
AU - Børte, Sigrid
AU - Chasman, Daniel I.
AU - Cherkas, Lynn
AU - Christensen, Anne Francke
AU - Cormand, Bru
AU - Cuenca-Leon, Ester
AU - Davey-Smith, George
AU - Dichgans, Martin
AU - van Duijn, Cornelia
AU - Eising, Else
AU - Esko, Tonu
AU - Esserlind, Ann Louise
AU - Ferrari, Michel
AU - Frants, Rune R.
AU - Freilinger, Tobias
AU - Furlotte, Nick
AU - Griffiths, Lyn
AU - Hamalainen, Eija
AU - Hansen, Thomas Folkmann
AU - Hiekkala, Marjo
AU - Arfan Ikram, M.
AU - Ingason, Andres
AU - Järvelin, Marjo Riitta
AU - Kajanne, Risto
AU - Kallela, Mikko
AU - Kaprio, Jaakko
AU - Kaunisto, Mari
AU - Kubisch, Christian
AU - Kurki, Mitja
AU - Olesen, Jes
AU - International Headache Genetics Consortium
N1 - Publisher Copyright: © 2017 Winsvold et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2017
Y1 - 2017
N2 - Migraine is a recurrent pain condition traditionally viewed as a neurovascular disorder, but little is known of its vascular basis. In epidemiological studies migraine is associated with an increased risk of cardiovascular disease, including coronary artery disease (CAD), suggesting shared pathogenic mechanisms. This study aimed to determine the genetic overlap between migraine and CAD, and to identify shared genetic risk loci, utilizing a conditional false discovery rate approach and data from two large-scale genome-wide association studies (GWAS) of CAD (C4D, 15,420 cases, 15,062 controls; CARDIoGRAM, 22,233 cases, 64,762 controls) and one of migraine (22,120 cases, 91,284 controls). We found significant enrichment of genetic variants associated with CAD as a function of their association with migraine, which was replicated across two independent CAD GWAS studies. One shared risk locus in the PHACTR1 gene (conjunctional false discovery rate for index SNP rs9349379 < 3.90 x 10−5), which was also identified in previous studies, explained much of the enrichment. Two further loci (in KCNK5 and AS3MT) showed evidence for shared risk (conjunctional false discovery rate < 0.05). The index SNPs at two of the three loci had opposite effect directions in migraine and CAD. Our results confirm previous reports that migraine and CAD share genetic risk loci in excess of what would be expected by chance, and highlight one shared risk locus in PHACTR1. Understanding the biological mechanisms underpinning this shared risk is likely to improve our understanding of both disorders.
AB - Migraine is a recurrent pain condition traditionally viewed as a neurovascular disorder, but little is known of its vascular basis. In epidemiological studies migraine is associated with an increased risk of cardiovascular disease, including coronary artery disease (CAD), suggesting shared pathogenic mechanisms. This study aimed to determine the genetic overlap between migraine and CAD, and to identify shared genetic risk loci, utilizing a conditional false discovery rate approach and data from two large-scale genome-wide association studies (GWAS) of CAD (C4D, 15,420 cases, 15,062 controls; CARDIoGRAM, 22,233 cases, 64,762 controls) and one of migraine (22,120 cases, 91,284 controls). We found significant enrichment of genetic variants associated with CAD as a function of their association with migraine, which was replicated across two independent CAD GWAS studies. One shared risk locus in the PHACTR1 gene (conjunctional false discovery rate for index SNP rs9349379 < 3.90 x 10−5), which was also identified in previous studies, explained much of the enrichment. Two further loci (in KCNK5 and AS3MT) showed evidence for shared risk (conjunctional false discovery rate < 0.05). The index SNPs at two of the three loci had opposite effect directions in migraine and CAD. Our results confirm previous reports that migraine and CAD share genetic risk loci in excess of what would be expected by chance, and highlight one shared risk locus in PHACTR1. Understanding the biological mechanisms underpinning this shared risk is likely to improve our understanding of both disorders.
U2 - 10.1371/journal.pone.0185663
DO - 10.1371/journal.pone.0185663
M3 - Journal article
C2 - 28957430
AN - SCOPUS:85032952518
VL - 12
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 9
M1 - e0185663
ER -
ID: 309204389