Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine
OA Location
Author(s)
Type
Journal Article
Abstract
Migraine is a debilitating neurological disorder affecting around one in seven people worldwide, but its molecular mechanisms remain poorly understood. There is some debate about whether migraine is a disease of vascular dysfunction or a result of neuronal dysfunction with secondary vascular changes. Genome-wide association (GWA) studies have thus far identified 13 independent loci associated with migraine. To identify new susceptibility loci, we carried out a genetic study of migraine on 59,674 affected subjects and 316,078 controls from 22 GWA studies. We identified 44 independent single-nucleotide polymorphisms (SNPs) significantly associated with migraine risk (P < 5 × 10−8) that mapped to 38 distinct genomic loci, including 28 loci not previously reported and a locus that to our knowledge is the first to be identified on chromosome X. In subsequent computational analyses, the identified loci showed enrichment for genes expressed in vascular and smooth muscle tissues, consistent with a predominant theory of migraine that highlights vascular etiologies.
Date Issued
2016-06-20
Date Acceptance
2016-05-26
Citation
Nature Genetics, 2016, 48 (8), pp.856-866
ISSN
1546-1718
Publisher
Nature Publishing Group
Start Page
856
End Page
866
Journal / Book Title
Nature Genetics
Volume
48
Issue
8
Subjects
Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
GENOME-WIDE ASSOCIATION
FAMILIAL HEMIPLEGIC MIGRAINE
SINGLE-NUCLEOTIDE POLYMORPHISMS
RECEPTOR-RELATED PROTEIN-1
SMOOTH-MUSCLE-CELLS
GENE-EXPRESSION
MYOCARDIAL-INFARCTION
SPREADING DEPRESSION
GENOTYPE IMPUTATION
SYSTEMATIC ANALYSIS
Publication Status
Published