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Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes

Journal article
Authors S. L. Pulit
L. C. Weng
P. F. McArdle
L. Trinquart
S. H. Choi
B. D. Mitchell
J. Rosand
P. I. W. de Bakker
E. J. Benjamin
P. T. Ellinor
S. J. Kittner
S. A. Lubitz
C. D. Anderson
I. E. Christophersen
M. Rienstra
C. Roselli
X. Y. Yin
B. Geelhoed
J. Barnard
H. H. Lin
D. E. Arking
A. V. Smith
C. M. Albert
M. Chaffin
N. R. Tucker
M. L. Li
D. Klarin
N. A. Bihlmeyer
S. K. Low
P. E. Weeke
M. Muller-Nurasyid
J. G. Smith
J. A. Brody
M. N. Niemeijer
M. Dorr
S. Trompet
J. Huffman
S. Gustafsson
C. Schurmann
M. E. Kleber
L. P. Lyytikainen
I. Seppala
R. Malik
Arvr Horimoto
M. Perez
J. Sinisalo
S. Aeschbacher
S. Theriault
J. Yao
F. Radmanesh
S. Weiss
A. Teumer
S. Clauss
R. Deo
D. J. Rader
S. Shah
A. Sun
J. C. Hopewell
S. Debette
G. Chauhan
Q. Yang
B. B. Worrall
G. Pare
Y. Kamatani
Y. P. Hagemeijer
N. Verweij
J. E. Siland
M. Kubo
J. D. Smith
D. R. Van Wagoner
J. C. Bis
S. Perz
B. M. Psaty
P. M. Ridker
J. W. Magnani
T. B. Harris
L. J. Launer
M. B. Shoemaker
S. Padmanabhan
J. Haessler
T. M. Bartz
M. Waldenberger
P. Lichtner
M. Arendt
J. E. Krieger
M. Kahonen
L. Risch
A. J. Mansur
A. Peters
B. H. Smith
L. Lind
S. A. Scott
Y. C. Lu
E. B. Bottinger
J. Hernesniemi
C. M. Lindgren
J. A. Wong
J. Huang
M. Eskola
A. P. Morris
I. Ford
A. P. Reiner
G. Delgado
L. Y. Chen
Y. D. I. Chen
R. K. Sandhu
M. Li
E. Boerwinkle
L. Eisele
L. Lannfelt
N. Rost
K. D. Taylor
A. Campbell
P. K. Magnusson
D. Porteous
L. J. Hocking
E. Vlachopoulou
N. L. Pedersen
K. Nikus
M. Orho-Melander
A. Hamsten
J. Heeringa
J. C. Denny
J. Kriebel
D. Darbar
C. Newton-Cheh
C. Shaffer
P. W. Macfarlane
S. Heilmann
P. Almgren
P. L. Huang
N. Sotoodehnia
E. Z. Soliman
A. G. Uitterlinden
A. Hofman
O. H. Franco
U. Volker
K. H. Jockel
M. F. Sinner
H. J. Lin
X. Q. Guo
M. Dichgans
E. Ingelsson
C. Kooperberg
O. Melander
R. J. F. Loos
J. Laurikka
D. Conen
P. van der Harst
M. L. Lokki
S. Kathiresan
A. Pereira
J. W. Jukema
C. Hayward
J. I. Rotter
W. Marz
T. Lehtimaki
B. H. Stricker
M. K. Chung
S. B. Felix
V. Gudnason
A. Alonso
D. M. Roden
S. Kaab
D. I. Chasman
S. R. Heckbert
T. Tanaka
K. L. Lunetta
S. Smoller
J. Sorkin
X. W. Wang
M. Selim
A. Pikula
P. Wolf
S. Seshadri
P. de Bakker
D. Chasman
K. Rexrode
I. Chen
J. Rotter
M. Luke
M. Sale
T. H. Lee
K. C. Chang
M. Elkind
L. Goldstein
M. L. James
M. Breteler
C. O'Donnell
D. Leys
C. Carty
C. Kidwell
J. Olesen
P. Sharma
S. Rich
T. Tatlisumak
O. Happola
P. Bijlenga
C. Soriano
E. Giralt
J. Roquer
J. Jimenez-Conde
I. Cotlarcius
J. Hardy
M. Korostynski
G. Boncoraglio
E. Ballabio
E. Parati
A. Mateusz
A. Urbanik
T. Dziedzic
J. Jagiella
J. Gasowski
M. Wnuk
R. Olszanecki
J. Pera
A. Slowik
K. J. Juchniewicz
C. Levi
P. Nyquist
I. Cendes
N. Cabral
P. Franca
A. Goncalves
L. Keller
M. Crisby
K. Kostulas
R. Lemmens
K. Ahmadi
C. Opherk
M. Duering
M. Gonik
J. Staals
P. Burri
A. Sadr-Nabavi
J. Romero
A. Biffi
C. Anderson
G. Falcone
B. Brouwers
R. Du
C. Kourkoulis
T. Battey
S. Lubitz
B. Mueller-Myhsok
J. Meschia
T. Brott
A. Pichler
C. Enzinger
H. Schmidt
R. Schmidt
S. Seiler
S. Blanton
Y. Yamada
A. Bersano
T. Rundek
R. Sacco
Y. F. Y. Chan
A. Gschwendtner
Z. Deng
T. Barr
K. Gwinn
R. Corriveau
A. Singleton
S. Waddy
L. Launer
C. Chen
K. E. Le
W. L. Lee
E. K. Tan
A. Olugbodi
P. Rothwell
S. Schilling
V. Mok
E. Lebedeva
C. Jern
K. Jood
S. Olsson
H. Kim
C. Lee
L. Kilarski
H. Markus
J. Peycke
S. Bevan
W. Sheu
H. Y. Chiou
J. Chern
E. Giraldo
M. Taqi
V. Jain
O. Lam
G. Howard
D. Woo
S. Kittner
B. Mitchell
J. Cole
J. O'Connell
D. Milewicz
K. Illoh
B. Worrall
C. Stine
B. Karaszewski
D. Werring
R. Sofat
J. Smalley
A. Lindgren
B. Hansen
B. Norrving
G. Smith
J. J. Martin
V. Thijs
K. Klijn
F. van't Hof
A. Algra
M. Macleod
R. Perry
D. Arnett
A. Pezzini
A. Padovani
S. Cramer
M. Fisher
D. Saleheen
J. Broderick
B. Kissela
A. Doney
C. Sudlow
K. Rannikmae
S. Silliman
C. McDonough
M. Walters
Annie Pedersen
K. Nakagawa
C. Chang
M. Dobbins
P. McArdle
Y. C. Chang
R. Brown
D. Brown
E. Holliday
R. Kalaria
J. Maguire
J. Attia
M. Farrall
A. K. Giese
M. Fornage
J. Majersik
M. Cushman
K. Keene
S. Bennett
D. Tirschwell
B. Psaty
A. Reiner
W. Longstreth
D. Spence
J. Montaner
I. Fernandez-Cadenas
C. Langefeld
C. Bushnell
L. Heitsch
J. M. Lee
K. Sheth
Consortium Atrial Fibrillation Genetics Conso; Int Stroke Genetics
Published in Neurology-Genetics
Volume 4
Issue 6
ISSN 2376-7839
Publication year 2018
Published at Institute of Biomedicine
Language en
Links dx.doi.org/10.1212/nxg.000000000000...
Keywords ischemic-stroke, causative classification, lifetime risk, epidemiology, association, prevention, variants, aspirin, burden, Neurosciences & Neurology
Subject categories Neurosciences

Abstract

Objective We sought to assess whether genetic risk factors for atrial fibrillation (AF) can explain cardioembolic stroke risk. We evaluated genetic correlations between a previous genetic study of AF and AF in the presence of cardioembolic stroke using genome-wide genotypes from the Stroke Genetics Network (N = 3,190 AF cases, 3,000 cardioembolic stroke cases, and 28,026 referents). We tested whether a previously validated AF polygenic risk score (PRS) associated with cardioembolic and other stroke subtypes after accounting for AF clinical risk factors. We observed a strong correlation between previously reported genetic risk for AF, AF in the presence of stroke, and cardioembolic stroke (Pearson r = 0.77 and 0.76, respectively, across SNPs with p < 4.4 x 10(-4) in the previous AF meta-analysis). An AF PRS, adjusted for clinical AF risk factors, was associated with cardioembolic stroke (odds ratio [OR] per SD = 1.40, p = 1.45 x 10(-48)), explaining similar to 20% of the heritable component of cardioembolic stroke risk. The AF PRS was also associated with stroke of undetermined cause (OR per SD = 1.07,p = 0.004), but no other primary stroke subtypes (all p > 0.1). Genetic risk of AF is associated with cardioembolic stroke, independent of clinical risk factors. Studies are warranted to determine whether AF genetic risk can serve as a biomarker for strokes caused by AF.

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