Genome-wide association study of white blood cell counts in ischemic stroke patients

Torres-Aguila, N.; Carrera, C.; Giese, A.K.; Cullell, N.; Muiño, E.; Cárcel-Márquez, J.; Gallego-Fabrega, C.; González-Sánchez, J.; Freijo, M.M.; Álvarez-Sabín, J.; Molina, C.; Ribo, M.; Jiménez-Conde, J.; Roquer, J.; Sobrino, T.; Campos, F.; Castillo, J.; Muñoz-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.; Martí-Fàbregas, J.; Heitsch, L.; Ibanez, L.; Cruchaga, C.; Rost, N.; Montaner, J.; Lee, J.M.; Fernandez-Cadenas, I.

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Genome-wide association study of white blood cell counts in ischemic stroke patients

Torres-Aguila, N.; Carrera, C.; Giese, A.K.; Cullell, N.; Muiño, E.; Cárcel-Márquez, J.; Gallego-Fabrega, C.; González-Sánchez, J.; Freijo, M.M.; Álvarez-Sabín, J.; Molina, C.; Ribo, M.; Jiménez-Conde, J.; Roquer, J.; Sobrino, T.; Campos, F.; Castillo, J.; Muñoz-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.; Martí-Fàbregas, J.; Heitsch, L.; Ibanez, L.; Cruchaga, C.; Rost, N.; Montaner, J.; Lee, J.M.; Fernandez-Cadenas, I.

URI: http://hdl.handle.net/11201/164471

Abstract:

Background and Purpose Immune cells play a key role in the first 24h post-stroke (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 (GWAS) and gene expression studies were performed. Results Our GWAS, which included 2,064 (Discovery) and 407 (Replication) patients, revealed a new locus (14q24.3) associated with leukocyte counts. After Joint analysis (n=2,471) five 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 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 to healthy conditions.