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


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.

SUBMITTER: Gormley P 

PROVIDER: S-EPMC5331903 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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

Gormley Padhraig P   Anttila Verneri V   Winsvold Bendik S BS   Palta Priit P   Esko Tonu T   Pers Tune H TH   Farh Kai-How KH   Cuenca-Leon Ester E   Muona Mikko M   Furlotte Nicholas A NA   Kurth Tobias T   Ingason Andres A   McMahon George G   Ligthart Lannie L   Terwindt Gisela M GM   Kallela Mikko M   Freilinger Tobias M TM   Ran Caroline C   Gordon Scott G SG   Stam Anine H AH   Steinberg Stacy S   Borck Guntram G   Koiranen Markku M   Quaye Lydia L   Adams Hieab H H HH   Lehtimäki Terho T   Sarin Antti-Pekka AP   Wedenoja Juho J   Hinds David A DA   Buring Julie E JE   Schürks Markus M   Ridker Paul M PM   Hrafnsdottir Maria Gudlaug MG   Stefansson Hreinn H   Ring Susan M SM   Hottenga Jouke-Jan JJ   Penninx Brenda W J H BW   Färkkilä Markus M   Artto Ville V   Kaunisto Mari M   Vepsäläinen Salli S   Malik Rainer R   Heath Andrew C AC   Madden Pamela A F PA   Martin Nicholas G NG   Montgomery Grant W GW   Kurki Mitja I MI   Kals Mart M   Mägi Reedik R   Pärn Kalle K   Hämäläinen Eija E   Huang Hailiang H   Byrnes Andrea E AE   Franke Lude L   Huang Jie J   Stergiakouli Evie E   Lee Phil H PH   Sandor Cynthia C   Webber Caleb C   Cader Zameel Z   Muller-Myhsok Bertram B   Schreiber Stefan S   Meitinger Thomas T   Eriksson Johan G JG   Salomaa Veikko V   Heikkilä Kauko K   Loehrer Elizabeth E   Uitterlinden Andre G AG   Hofman Albert A   van Duijn Cornelia M CM   Cherkas Lynn L   Pedersen Linda M LM   Stubhaug Audun A   Nielsen Christopher S CS   Männikkö Minna M   Mihailov Evelin E   Milani Lili L   Göbel Hartmut H   Esserlind Ann-Louise AL   Christensen Anne Francke AF   Hansen Thomas Folkmann TF   Werge Thomas T   Kaprio Jaakko J   Aromaa Arpo J AJ   Raitakari Olli O   Ikram M Arfan MA   Spector Tim T   Järvelin Marjo-Riitta MR   Metspalu Andres A   Kubisch Christian C   Strachan David P DP   Ferrari Michel D MD   Belin Andrea C AC   Dichgans Martin M   Wessman Maija M   van den Maagdenberg Arn M J M AM   Zwart John-Anker JA   Boomsma Dorret I DI   Smith George Davey GD   Stefansson Kari K   Eriksson Nicholas N   Daly Mark J MJ   Neale Benjamin M BM   Olesen Jes J   Chasman Daniel I DI   Nyholt Dale R DR   Palotie Aarno A  

Nature genetics 20160620 8


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  ...[more]

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