Genome-Wide Association Study of White Blood Cell Counts in Patients With Ischemic Stroke
Por:
Torres-Aguila, NP, Carrera, C, Giese, AK, Cullell, N, Muino, E, Carcel-Marquez, J, Gallego-Fabrega, C, Gonzalez-Sanchez, J, Freijo, MD, Alvarez-Sabin, J, Molina, C, Ribo, M, Jimenez-Conde, J, Roquer, J, Sobrino, T, Campos, F, Castillo, J, Munoz-Narbona, L, Lopez-Cancio, E, Davalos, A, Diaz-Navarro, R, Tur, S, Vives-Bauza, C, Serrano-Heras, G, Segura, T, Krupinski, J, Delgado-Mederos, R, Marti-Fabregas, J, Heitsch, L, Ibanez, L, Cruchaga, C, Rost, NS, Montaner, J, Lee, JM and Fernandez-Cadenas, I
Publicada:
1 dic 2019
Ahead of Print:
7 oct 2019
Resumen:
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.
Filiaciones:
Torres-Aguila, NP:
Hosp Santa Creu & Sant Pau, Stroke Pharmacogen & Genet Lab, Res Inst, Carrer St Antoni Maria Claret 167, Barcelona 08025, Spain
Vall dHebron Res Inst, Neurovasc Res Lab, Barcelona, Spain
Carrera, C:
Vall dHebron Res Inst, Neurovasc Res Lab, Barcelona, Spain
Giese, AK:
Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA
Cullell, N:
Hosp Univ Mutua Terrassa, Stroke Pharmacogen & Genet Lab, Fundacio Mutua Terrasa, Terrassa, Spain
Muino, E:
Hosp Santa Creu & Sant Pau, Stroke Pharmacogen & Genet Lab, Res Inst, Carrer St Antoni Maria Claret 167, Barcelona 08025, Spain
Carcel-Marquez, J:
Hosp Santa Creu & Sant Pau, Stroke Pharmacogen & Genet Lab, Res Inst, Carrer St Antoni Maria Claret 167, Barcelona 08025, Spain
Gallego-Fabrega, C:
Hosp Santa Creu & Sant Pau, Stroke Pharmacogen & Genet Lab, Res Inst, Carrer St Antoni Maria Claret 167, Barcelona 08025, Spain
Hosp Univ Mutua Terrassa, Stroke Pharmacogen & Genet Lab, Fundacio Mutua Terrasa, Terrassa, Spain
Gonzalez-Sanchez, J:
Hosp Santa Creu & Sant Pau, Stroke Pharmacogen & Genet Lab, Res Inst, Carrer St Antoni Maria Claret 167, Barcelona 08025, Spain
Hosp Univ Mutua Terrassa, Stroke Pharmacogen & Genet Lab, Fundacio Mutua Terrasa, Terrassa, Spain
Manchester Metropolitan Univ, Sch Healthcare Sci, Manchester, Lancs, England
Freijo, MD:
Hosp Basurto, Neurol Dept, Bilbao, Spain
Alvarez-Sabin, J:
Hosp Univ Vall dHebron, Neurol Dept, Stroke Unit, Barcelona, Spain
Molina, C:
Hosp Univ Vall dHebron, Neurol Dept, Stroke Unit, Barcelona, Spain
Ribo, M:
Hosp Univ Vall dHebron, Neurol Dept, Stroke Unit, Barcelona, Spain
Jimenez-Conde, J:
Hosp Mar Barcelona, Neurol Dept, Inst Hosp Mar Invest Med, Barcelona, Spain
Inst Hosp Mar Invest Med, Neurovasc Res Grp, Barcelona, Spain
Univ Autonoma Barcelona, Dept Ciencias Expt & Salud, Univ Pompeu Fabra, Barcelona, Spain
Roquer, J:
Hosp Mar Barcelona, Neurol Dept, Inst Hosp Mar Invest Med, Barcelona, Spain
Inst Hosp Mar Invest Med, Neurovasc Res Grp, Barcelona, Spain
Univ Autonoma Barcelona, Dept Ciencias Expt & Salud, Univ Pompeu Fabra, Barcelona, Spain
Sobrino, T:
Inst Invest Sanitaria Santiago de Compostela, Clin Neurosci Res Lab, Santiago De Compostela, Spain
Campos, F:
Inst Invest Sanitaria Santiago de Compostela, Clin Neurosci Res Lab, Santiago De Compostela, Spain
Castillo, J:
Inst Invest Sanitaria Santiago de Compostela, Clin Neurosci Res Lab, Santiago De Compostela, Spain
:
Univ Autonoma Barcelona, Neurosci Dept, Hosp Germans Triers & Pujol, Barcelona, Spain
Lopez-Cancio, E:
Hosp Univ Cent Asturias, Stroke Unit, Oviedo, Spain
:
Univ Autonoma Barcelona, Neurosci Dept, Hosp Germans Triers & Pujol, Barcelona, Spain
Diaz-Navarro, R:
Fundacio Inst Invest Sanitaria Illes Balears, Neurosci Lab, Mallorca, Spain
Tur, S:
Fundacio Inst Invest Sanitaria Illes Balears, Neurosci Lab, Mallorca, Spain
Vives-Bauza, C:
Fundacio Inst Invest Sanitaria Illes Balears, Neurosci Lab, Mallorca, Spain
Serrano-Heras, G:
Univ Hosp Albacete, Neurol Dept, Albacete, Spain
Segura, T:
Univ Hosp Albacete, Neurol Dept, Albacete, Spain
Krupinski, J:
Manchester Metropolitan Univ, Sch Healthcare Sci, Manchester, Lancs, England
Hosp Univ Mutua Terrassa, Neurol Serv, Terrassa, Spain
Delgado-Mederos, R:
Hosp Santa Creu & Sant Pau, Neurol Dept, Stroke Unit, Barcelona, Spain
Marti-Fabregas, J:
Hosp Santa Creu & Sant Pau, Neurol Dept, Stroke Unit, Barcelona, Spain
Heitsch, L:
Washington Univ, Sch Med, Emergency Med, St Louis, MO USA
Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA
Ibanez, L:
Washington Univ, Sch Med, Dept Psychiat, St Louis, MO USA
Cruchaga, C:
Washington Univ, Sch Med, Dept Psychiat, St Louis, MO USA
Rost, NS:
Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA
Montaner, J:
Vall dHebron Res Inst, Neurovasc Res Lab, Barcelona, Spain
Univ Seville, Inst Biomed Sevilla, Stroke Res Program, CSIC,Hosp Univ Virgen Rocio, Seville, Spain
Hosp Univ Virgen Macarena, Dept Neurol, Seville, Spain
Lee, JM:
Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA
Fernandez-Cadenas, I:
Hosp Santa Creu & Sant Pau, Stroke Pharmacogen & Genet Lab, Res Inst, Carrer St Antoni Maria Claret 167, Barcelona 08025, Spain
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