Shared genetic basis for migraine and ischemic stroke: A genome-wide analysis of common variants.
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.
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Rainer
R
Malik
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Tobias
T
Freilinger
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Bendik S
BS
Winsvold
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Verneri
V
Anttila
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Jason
J
Vander Heiden
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Matthew
M
Traylor
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Boukje
B
de Vries
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Elizabeth G
EG
Holliday
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Gisela M
GM
Terwindt
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Jonathan
J
Sturm
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Joshua C
JC
Bis
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Jemma C
JC
Hopewell
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Michel D
MD
Ferrari
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Kristiina
K
Rannikmae
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Maija
M
Wessman
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Mikko
M
Kallela
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Christian
C
Kubisch
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Myriam
M
Fornage
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James F
JF
Meschia
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Terho
T
Lehtimäki
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Cathie
C
Sudlow
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Robert
R
Clarke
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Daniel I
DI
Chasman
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Braxton D
BD
Mitchell
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Jane
J
Maguire
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Jaakko
J
Kaprio
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Martin
M
Farrall
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Olli T
OT
Raitakari
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Tobias
T
Kurth
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M Arfan
MA
Ikram
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Alex P
AP
Reiner
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W T
WT
Longstreth
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Peter M
PM
Rothwell
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David P
DP
Strachan
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Pankaj
P
Sharma
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Sudha
S
Seshadri
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Lydia
L
Quaye
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Lynn
L
Cherkas
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Markus
M
Schürks
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Jonathan
J
Rosand
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Lannie
L
Ligthart
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Giorgio B
GB
Boncoraglio
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George
G
Davey Smith
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Cornelia M
CM
van Duijn
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Kari
K
Stefansson
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Bradford B
BB
Worrall
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Dale R
DR
Nyholt
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Hugh S
HS
Markus
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Arn M J M
AM
van den Maagdenberg
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Chris
C
Cotsapas
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John A
JA
Zwart
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Aarno
A
Palotie
Author affiliations are provided at the end of the article. martin.dichgans@med.uni-muenchen.de.
Martin
M
Dichgans
D002545:Brain Ischemia / Q000453:epidemiology / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D020325:Migraine with Aura / Q000453:epidemiology / Q000235:genetics*; D020326:Migraine without Aura / Q000453:epidemiology / Q000235:genetics*; D020521:Stroke / Q000453:epidemiology / Q000235:genetics*