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

PLoS One
Authors
Keywords
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.

Year of Publication
2017
Journal
PLoS One
Volume
12
Issue
9
Pages
e0185663
Date Published
2017
ISSN
1932-6203
DOI
10.1371/journal.pone.0185663
PubMed ID
28957430
PubMed Central ID
PMC5619824
Links
Grant list
G1001799 / MRC_ / Medical Research Council / United Kingdom
MR/N01104X/1 / MRC_ / Medical Research Council / United Kingdom
MR/N01104X/2 / MRC_ / Medical Research Council / United Kingdom
R21 NS092963 / NS / NINDS NIH HHS / United States