TY - JOUR
T1 - Genome-wide association study of white blood cell counts in patients with ischemic stroke
AU - Torres-Aguila, Nuria P
AU - Carrera, Caty
AU - Giese, Anne-Katrine
AU - Cullell, Natalia
AU - Muiño, Elena
AU - Cárcel-Márquez, Jara
AU - Gallego-Fabrega, Cristina
AU - González-Sánchez, Jonathan
AU - Del Mar Freijo, María
AU - Álvarez-Sabín, José
AU - Molina, Carlos
AU - Ribó, Marc
AU - Jimenez-Conde, Jordi
AU - Roquer, Jaume
AU - Sobrino, Tomás
AU - Campos, Francisco
AU - Castillo, José
AU - Muñoz-Narbona, Lucia
AU - Lopez-Cancio, Elena
AU - Dàvalos, Antoni
AU - Diaz-Navarro, Rosa
AU - Tur, Silvia
AU - Vives-Bauza, Cristòfol
AU - Serrano-Heras, Gemma
AU - Segura, Tomás
AU - Krupinski, Jerzy
AU - Delgado-Mederos, Raquel
AU - Martí-Fàbregas, Joan
AU - Heitsch, Laura
AU - Ibañez, Laura
AU - Cruchaga, Carlos
AU - Rost, Natalia S
AU - Montaner, Joan
AU - Lee, Jin-Moo
AU - Fernandez-Cadenas, Israel
PY - 2019/12
Y1 - 2019/12
N2 - 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<5×10-8). 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.
AB - 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<5×10-8). 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.
KW - Aged
KW - Aged, 80 and over
KW - Brain Ischemia/genetics
KW - Chromosomes, Human, Pair 14/genetics
KW - Female
KW - Genome-Wide Association Study
KW - Humans
KW - Leukocyte Count
KW - Leukocytes/immunology
KW - Male
KW - Middle Aged
KW - Polymorphism, Single Nucleotide
KW - Prognosis
KW - Stroke/genetics
U2 - 10.1161/STROKEAHA.119.026593
DO - 10.1161/STROKEAHA.119.026593
M3 - Article
C2 - 31587654
SN - 0039-2499
VL - 50
SP - 3618
EP - 3621
JO - Stroke
JF - Stroke
IS - 12
ER -