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Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine

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  • Padhraig Gormley
  • Verneri Anttila
  • Bendik S Winsvold
  • Priit Palta
  • Tonu Esko
  • Tune H Pers
  • Kai-How Farh
  • Ester Cuenca-Leon
  • Mikko Muona
  • Nicholas A Furlotte
  • Tobias Kurth
  • Andres Ingason
  • George McMahon
  • Lannie Ligthart
  • Gisela M Terwindt
  • Mikko Kallela
  • Tobias M Freilinger
  • Caroline Ran
  • Scott G Gordon
  • Anine H Stam
  • Stacy Steinberg
  • Guntram Borck
  • Markku Koiranen
  • Lydia Quaye
  • Hieab H H Adams
  • Terho Lehtimäki
  • Antti-Pekka Sarin
  • Juho Wedenoja
  • David A Hinds
  • Julie E Buring
  • Markus Schürks
  • Paul M Ridker
  • Maria Gudlaug Hrafnsdottir
  • Hreinn Stefansson
  • Susan M Ring
  • Jouke-Jan Hottenga
  • Brenda W J H Penninx
  • Markus Färkkilä
  • Ville Artto
  • Mari Kaunisto
  • Salli Vepsäläinen
  • Rainer Malik
  • Andrew C Heath
  • Pamela A F Madden
  • Nicholas G Martin
  • Ann-Louise Esserlind
  • Anne Francke Christensen
  • Thomas Folkmann Hansen
  • Thomas Werge
  • Jes Olesen
  • International Headache Genetics Consortium
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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.

Original languageEnglish
JournalNature Genetics
Volume48
Issue number8
Pages (from-to)856-66
Number of pages11
ISSN1061-4036
DOIs
Publication statusPublished - Aug 2016

    Research areas

  • Journal Article

ID: 49003033