Genome-Wide Association Study of White Blood Cell Counts in Patients With Ischemic Stroke

被引：11

作者：

Torres-Aguila, Nuria P. ^{[1
,2
]}

Carrera, Caty ^{[2
]}

Giese, Anne-Katrine ^{[3
]}

Cullell, Natalia ^{[4
]}

Muino, Elena ^{[1
]}

Carcel-Marquez, Jara ^{[1
]}

Gallego-Fabrega, Cristina ^{[1
,4
]}

Gonzalez-Sanchez, Jonathan ^{[1
,4
,5
]}

Freijo, Maria del Mar ^{[6
]}

Alvarez-Sabin, Jose ^{[7
]}

Molina, Carlos ^{[7
]}

Ribo, Marc ^{[7
]}

Jimenez-Conde, Jordi ^{[8
,9
,10
]}

Roquer, Jaume ^{[8
,9
,10
]}

Sobrino, Tomas ^{[11
]}

Campos, Francisco ^{[11
]}

Castillo, Jose ^{[11
]}

Munoz-Narbona, Lucia ^{[12
]}

Lopez-Cancio, Elena ^{[13
]}

Davalos, Antoni ^{[12
]}

Diaz-Navarro, Rosa ^{[14
]}

Tur, Silvia ^{[14
]}

Vives-Bauza, Cristofol ^{[14
]}

Serrano-Heras, Gemma ^{[15
]}

Segura, Tomas ^{[15
]}

Krupinski, Jerzy ^{[5
,16
]}

Delgado-Mederos, Raquel ^{[17
]}

Marti-Fabregas, Joan ^{[17
]}

Heitsch, Laura ^{[18
,19
]}

Ibanez, Laura ^{[20
]}

Cruchaga, Carlos ^{[20
]}

Rost, Natalia S. ^{[3
]}

Montaner, Joan ^{[2
,21
,22
]}

Lee, Jin-Moo ^{[19
]}

Fernandez-Cadenas, Israel ^{[1
]}

机构：

[1] Hosp Santa Creu & Sant Pau, Stroke Pharmacogen & Genet Lab, Res Inst, Carrer St Antoni Maria Claret 167, Barcelona 08025, Spain

[2] Vall dHebron Res Inst, Neurovasc Res Lab, Barcelona, Spain

[3] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA

[4] Hosp Univ Mutua Terrassa, Stroke Pharmacogen & Genet Lab, Fundacio Mutua Terrasa, Terrassa, Spain

[5] Manchester Metropolitan Univ, Sch Healthcare Sci, Manchester, Lancs, England

[6] Hosp Basurto, Neurol Dept, Bilbao, Spain

[7] Hosp Univ Vall dHebron, Neurol Dept, Stroke Unit, Barcelona, Spain

[8] Hosp Mar Barcelona, Neurol Dept, Inst Hosp Mar Invest Med, Barcelona, Spain

[9] Inst Hosp Mar Invest Med, Neurovasc Res Grp, Barcelona, Spain

[10] Univ Autonoma Barcelona, Dept Ciencias Expt & Salud, Univ Pompeu Fabra, Barcelona, Spain

[11] Inst Invest Sanitaria Santiago de Compostela, Clin Neurosci Res Lab, Santiago De Compostela, Spain

[12] Univ Autonoma Barcelona, Neurosci Dept, Hosp Germans Triers & Pujol, Barcelona, Spain

[13] Hosp Univ Cent Asturias, Stroke Unit, Oviedo, Spain

[14] Fundacio Inst Invest Sanitaria Illes Balears, Neurosci Lab, Mallorca, Spain

[15] Univ Hosp Albacete, Neurol Dept, Albacete, Spain

[16] Hosp Univ Mutua Terrassa, Neurol Serv, Terrassa, Spain

[17] Hosp Santa Creu & Sant Pau, Neurol Dept, Stroke Unit, Barcelona, Spain

[18] Washington Univ, Sch Med, Emergency Med, St Louis, MO USA

[19] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA

[20] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO USA

[21] Univ Seville, Inst Biomed Sevilla, Stroke Res Program, CSIC,Hosp Univ Virgen Rocio, Seville, Spain

[22] Hosp Univ Virgen Macarena, Dept Neurol, Seville, Spain

来源：

STROKE | 2019年 / 50卷 / 12期

基金：

美国国家卫生研究院;

关键词：

genome-wide association study; humans; leukocytes; risk factors; stroke;

D O I：

10.1161/STROKEAHA.119.026593

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background and Purpose-Immune cells play a key role in the first 24h poststroke (acute phase), being associated with stroke outcome. We aimed to find genetic risk factors associated with leukocyte counts during the acute phase of stroke. Methods-Ischemic stroke patients with leukocyte counts data during the first 24h were included. Genome-wide association study and gene expression studies were performed. Results-Our genome-wide association study, which included 2064 (Discovery) and 407 (Replication) patients, revealed a new locus (14q24.3) associated with leukocyte counts. After Joint analysis (n=2471) 5 more polymorphisms reached genome-wide significance (P<5x10(-8)). The 14q24.3 locus was associated with acute stroke outcome (rs112809786, P=0.036) and with ACOT1 and PTGR2 gene expression. Previous polymorphisms associated with leukocyte counts in general-population did not show any significance in our study. Conclusions-We have found the first locus associated with leukocyte counts in ischemic stroke, also associated with acute outcome. Genetic analysis of acute endophenotypes could be useful to find the genetic factors associated with stroke outcome. Our findings suggested a different modulation of immune cells in stroke compared with healthy conditions.

引用

页码：3618 / 3621

页数：4

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