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. 2015 Jul 2;1(1):e10.
doi: 10.1212/NXG.0000000000000010. eCollection 2015 Jun.

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

Bendik S Winsvold  1 , Christopher P Nelson  1 , Rainer Malik  1 , Padhraig Gormley  1 , Verneri Anttila  1 , Jason Vander Heiden  1 , Katherine S Elliott  1 , Line M Jacobsen  1 , Priit Palta  1 , Najaf Amin  1 , Boukje de Vries  1 , Eija Hämäläinen  1 , Tobias Freilinger  1 , M Arfan Ikram  1 , Thorsten Kessler  1 , Markku Koiranen  1 , Lannie Ligthart  1 , George McMahon  1 , Linda M Pedersen  1 , Christina Willenborg  1 , Hong-Hee Won  1 , Jes Olesen  1 , Ville Artto  1 , Themistocles L Assimes  1 , Stefan Blankenberg  1 , Dorret I Boomsma  1 , Lynn Cherkas  1 , George Davey Smith  1 , Stephen E Epstein  1 , Jeanette Erdmann  1 , Michel D Ferrari  1 , Hartmut Göbel  1 , Alistair S Hall  1 , Marjo-Riitta Jarvelin  1 , Mikko Kallela  1 , Jaakko Kaprio  1 , Sekar Kathiresan  1 , Terho Lehtimäki  1 , Ruth McPherson  1 , Winfried März  1 , Dale R Nyholt  1 , Christopher J O'Donnell  1 , Lydia Quaye  1 , Daniel J Rader  1 , Olli Raitakari  1 , Robert Roberts  1 , Heribert Schunkert  1 , Markus Schürks  1 , Alexandre F R Stewart  1 , Gisela M Terwindt  1 , Unnur Thorsteinsdottir  1 , Arn M J M van den Maagdenberg  1 , Cornelia van Duijn  1 , Maija Wessman  1 , Tobias Kurth  1 , Christian Kubisch  1 , Martin Dichgans  1 , Daniel I Chasman  1 , Chris Cotsapas  1 , John-Anker Zwart  1 , Nilesh J Samani  1 , Aarno Palotie  1 ; CARDIoGRAM Consortium and the International Headache Genetics Consortium
Affiliations

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

Bendik S Winsvold et al. Neurol Genet. .

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.

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Figures

Figure 1
Figure 1. Study design and included cohorts
CPSM = Cross-Phenotype Spatial Mapping.
Figure 2
Figure 2. Association between coronary artery disease polygenic risk score and the presence of migraine
Results are given as odds ratios with 95% confidence intervals. Separate lines are shown for all migraine (blue), migraine without aura (green), and migraine with aura (red). The coronary artery disease (CAD) polygenic risk score was calculated based on single nucleotide polymorphisms (SNPs) with weak (p < 1 × 10−2), moderate (p < 1 × 10−4), or strong (p < 5 × 10−8) association to CAD in the Coronary ARtery DIsease Genome-Wide Replication And Meta-Analysis study.
See this image and copyright information in PMC

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