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PLoS One. 2017 Sep 28;12(9):e0185663. doi: 10.1371/journal.pone.0185663. eCollection 2017.

Shared genetic risk between migraine and coronary artery disease: A genome-wide analysis of common variants.

Author information

1
FORMI and Department of Neurology, Oslo University Hospital, Oslo, Norway.
2
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
3
NORMENT KG Jebsen Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
4
Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
5
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
6
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
7
Psychiatric & Neurodevelopmental Genetics Unit, Department of Psychiatry Massachusetts General Hospital, Boston, Massachusetts, United States of America.
8
Institute of Public Health, Charité-Universitätsmedizin Berlin, Berlin, Germany.
9
Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
10
Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands.
11
Department of Neurology and Epileptology, Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
12
Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany.
13
Center for Multimodal Imaging & Genetics, University of California, San Diego, La Jolla, California, United States of America.
14
Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands.
15
Harvard Medical School, Boston, Massachusetts, United States of America.
16
Statistical and Genomic Epidemiology Laboratory, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Australia.

Abstract

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.

PMID:
28957430
PMCID:
PMC5619824
DOI:
10.1371/journal.pone.0185663
[Indexed for MEDLINE]
Free PMC Article

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