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