Shared genetic basis for migraine and ischemic stroke

Rainer Malik, Tobias Freilinger, Bendik S. Winsvold, Verneri Anttila, Jason Vander Heiden, Matthew Traylor, Boukje De Vries, Elizabeth G. Holliday, Gisela M. Terwindt, Jonathan Sturm, Joshua C. Bis, Jemma C. Hopewell, Michel D. Ferrari, Kristiina Rannikmae, Maija Wessman, Mikko Kallela, Christian Kubisch, Myriam Fornage, James F. Meschia, Terho LehtimäkiCathie Sudlow, Robert Clarke, Daniel I. Chasman, Braxton D. Mitchell, Jane Maguire, Jaakko Kaprio, Martin Farrall, Olli T. Raitakari, Tobias Kurth, M. Arfan Ikram, Alex P. Reiner, W. T. Longstreth, Peter M. Rothwell, David P. Strachan, Pankaj Sharma, Sudha Seshadri, Lydia Quaye, Lynn Cherkas, Markus Schürks, Jonathan Rosand, Lannie Ligthart, Giorgio B. Boncoraglio, George Davey Smith, Cornelia M. Van Duijn, Kari Stefansson, Bradford B. Worrall, Dale R. Nyholt, Hugh S. Markus, Arn M.J.M. Van Den Maagdenberg, Chris Cotsapas, John A. Zwart, Aarno Palotie, Martin Dichgans

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Objective: To quantify genetic overlap between migraine and ischemic stroke (IS) with respect to common genetic variation. Methods: We applied 4 different approaches to large-scale meta-analyses of genome-wide data on migraine (23,285 cases and 95,425 controls) and IS (12,389 cases and 62,004 controls). First, we queried known genome-wide significant loci for both disorders, looking for potential overlap of signals. We then analyzed the overall shared genetic load using polygenic scores and estimated the genetic correlation between disease subtypes using data derived from these models. We further interrogated genomic regions of shared risk using analysis of covariance patterns between the 2 phenotypes using cross-phenotype spatial mapping. Results: We found substantial genetic overlap between migraine and IS using all 4 approaches. Migraine without aura (MO) showed much stronger overlap with IS and its subtypes than migraine with aura (MA). The strongest overlap existed between MO and large artery stroke (LAS; p 6.4 × 10-28 for the LAS polygenic score in MO) and between MO and cardioembolic stroke (CE; p 2.7 × 10-20 for the CE score in MO). Conclusions: Our findings indicate shared genetic susceptibility to migraine and IS, with a particularly strong overlap between MO and both LAS and CE pointing towards shared mechanisms. Our observations on MA are consistent with a limited role of common genetic variants in this subtype.

Original languageEnglish (US)
Pages (from-to)2132-2145
Number of pages14
JournalNeurology
Volume84
Issue number21
DOIs
StatePublished - May 26 2015
Externally publishedYes

ASJC Scopus subject areas

  • Clinical Neurology

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