RT Journal Article
SR Electronic
T1 Genetic analysis for a shared biological basis between migraine and coronary artery disease
JF Neurology Genetics
JO Neurol Genet
FD Lippincott Williams & Wilkins
SP e10
DO 10.1212/NXG.0000000000000010
VO 1
IS 1
A1 Winsvold, Bendik S.
A1 Nelson, Christopher P.
A1 Malik, Rainer
A1 Gormley, Padhraig
A1 Anttila, Verneri
A1 Vander Heiden, Jason
A1 Elliott, Katherine S.
A1 Jacobsen, Line M.
A1 Palta, Priit
A1 Amin, Najaf
A1 de Vries, Boukje
A1 Hämäläinen, Eija
A1 Freilinger, Tobias
A1 Ikram, M. Arfan
A1 Kessler, Thorsten
A1 Koiranen, Markku
A1 Ligthart, Lannie
A1 McMahon, George
A1 Pedersen, Linda M.
A1 Willenborg, Christina
A1 Won, Hong-Hee
A1 Olesen, Jes
A1 Artto, Ville
A1 Assimes, Themistocles L.
A1 Blankenberg, Stefan
A1 Boomsma, Dorret I.
A1 Cherkas, Lynn
A1 Davey Smith, George
A1 Epstein, Stephen E.
A1 Erdmann, Jeanette
A1 Ferrari, Michel D.
A1 Göbel, Hartmut
A1 Hall, Alistair S.
A1 Jarvelin, Marjo-Riitta
A1 Kallela, Mikko
A1 Kaprio, Jaakko
A1 Kathiresan, Sekar
A1 Lehtimäki, Terho
A1 McPherson, Ruth
A1 März, Winfried
A1 Nyholt, Dale R.
A1 O'Donnell, Christopher J.
A1 Quaye, Lydia
A1 Rader, Daniel J.
A1 Raitakari, Olli
A1 Roberts, Robert
A1 Schunkert, Heribert
A1 Schürks, Markus
A1 Stewart, Alexandre F.R.
A1 Terwindt, Gisela M.
A1 Thorsteinsdottir, Unnur
A1 van den Maagdenberg, Arn M.J.M.
A1 van Duijn, Cornelia
A1 Wessman, Maija
A1 Kurth, Tobias
A1 Kubisch, Christian
A1 Dichgans, Martin
A1 Chasman, Daniel I.
A1 Cotsapas, Chris
A1 Zwart, John-Anker
A1 Samani, Nilesh J.
A1 Palotie, Aarno
A1 ,
YR 2015
UL http://ng.neurology.org/content/1/1/e10.abstract
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.CAD=coronary artery disease; CARDIoGRAM=Coronary ARtery DIsease Genome-Wide Replication And Meta-Analysis; CPSM=Cross-Phenotype Spatial Mapping; GWAS=genome-wide association studies; IHGC=International Headache Genetics Consortium; LD=linkage disequilibrium; MA=migraine with aura; MO=migraine without aura; SNP=single nucleotide polymorphism