RT Journal Article
SR Electronic
T1 Shared genetic basis for migraine and ischemic stroke
JF Neurology
JO Neurology
FD Lippincott Williams & Wilkins
SP 2132
OP 2145
DO 10.1212/WNL.0000000000001606
VO 84
IS 21
A1 Malik, Rainer
A1 Freilinger, Tobias
A1 Winsvold, Bendik S.
A1 Anttila, Verneri
A1 Vander Heiden, Jason
A1 Traylor, Matthew
A1 de Vries, Boukje
A1 Holliday, Elizabeth G.
A1 Terwindt, Gisela M.
A1 Sturm, Jonathan
A1 Bis, Joshua C.
A1 Hopewell, Jemma C.
A1 Ferrari, Michel D.
A1 Rannikmae, Kristiina
A1 Wessman, Maija
A1 Kallela, Mikko
A1 Kubisch, Christian
A1 Fornage, Myriam
A1 Meschia, James F.
A1 Lehtimäki, Terho
A1 Sudlow, Cathie
A1 Clarke, Robert
A1 Chasman, Daniel I.
A1 Mitchell, Braxton D.
A1 Maguire, Jane
A1 Kaprio, Jaakko
A1 Farrall, Martin
A1 Raitakari, Olli T.
A1 Kurth, Tobias
A1 Ikram, M. Arfan
A1 Reiner, Alex P.
A1 Longstreth, W.T.
A1 Rothwell, Peter M.
A1 Strachan, David P.
A1 Sharma, Pankaj
A1 Seshadri, Sudha
A1 Quaye, Lydia
A1 Cherkas, Lynn
A1 Schürks, Markus
A1 Rosand, Jonathan
A1 Ligthart, Lannie
A1 Boncoraglio, Giorgio B.
A1 Davey Smith, George
A1 van Duijn, Cornelia M.
A1 Stefansson, Kari
A1 Worrall, Bradford B.
A1 Nyholt, Dale R.
A1 Markus, Hugh S.
A1 van den Maagdenberg, Arn M.J.M.
A1 Cotsapas, Chris
A1 Zwart, John A.
A1 Palotie, Aarno
A1 ,
A1 Dichgans, Martin
A1 ,
YR 2015
UL http://n.neurology.org/content/84/21/2132.abstract
AB 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.CE=cardioembolic stroke; CPSM=cross-phenotype spatial mapping; GWAS=genome-wide association studies; IHGC=International Headache Genetics Consortium; IS=ischemic stroke; LAS=large artery stroke; LD=linkage disequilibrium; MA=migraine with aura; MO=migraine without aura; SNP=single nucleotide polymorphism; SVD=small vessel disease