TY - JOUR
T1 - PATJ Low Frequency Variants Are Associated with Worse Ischemic Stroke Functional Outcome: A Genome-Wide Meta-Analysis
AU - Mola-Caminal, Marina
AU - Carrera, Caty
AU - Soriano-Tárraga, Carolina
AU - Giralt-Steinhauer, Eva
AU - Díaz-Navarro, Rosa M.
AU - Tur, Sílvia
AU - Jiménez, Carmen
AU - Medina-Dols, Aina
AU - Cullell, Natàlia
AU - Torres-Aguila, Nuria P.
AU - Muiño, Elena
AU - Rodríguez-Campello, Ana
AU - Ois, Angel
AU - Cuadrado-Godia, Elisa
AU - Vivanco-Hidalgo, Rosa M.
AU - Hernandez-Guillamon, Mar
AU - Solé, Montse
AU - Delgado, Pilar
AU - Bustamante, Alejandro
AU - García-Berrocoso, Teresa
AU - Mendióroz, Maite
AU - Castellanos, Mar
AU - Serena, Joaquín
AU - Martí-Fàbregas, Joan
AU - Segura, Tomás
AU - Serrano-Heras, Gemma
AU - Obach, Victor
AU - Ribó, Marc
AU - Molina, Carlos A.
AU - Alvarez-Sabín, José
AU - Palomeras, Ernest
AU - Freijo, Mar
AU - Font, Maria A.
AU - Rosand, Jonathan
AU - Rost, Natalia S.
AU - Gallego-Fabrega, Cristina
AU - Lee, Jin Moo
AU - Heitsch, Laura
AU - Ibanez, Laura
AU - Cruchaga, Carlos
AU - Phuah, Chia Ling
AU - Lemmens, Robin
AU - Thijs, Vincent
AU - Lindgren, Arne
AU - Maguire, Jane
AU - Rannikmae, Kristiina
AU - Sudlow, Catherine L.
AU - Jern, Christina
AU - Stanne, Tara M.
AU - Lorentzen, Erik
AU - Muñoz-Narbona, Lucía
AU - Dávalos, Antonio
AU - López-Cancio, Elena
AU - Worrall, Bradford B.
AU - Woo, Daniel
AU - Kittner, Steven J.
AU - Mitchell, Braxton D.
AU - Montaner, Joan
AU - Roquer, Jaume
AU - Krupinski, Jurek
AU - Estivill, Xavier
AU - Rabionet, Raquel
AU - Vives-Bauzá, Cristòfol
AU - Fernández-Cadenas, Israel
AU - Jimenez-Conde, Jordi
PY - 2019/1/4
Y1 - 2019/1/4
N2 - © 2018 American Heart Association, Inc. Rationale: Ischemic stroke is among the leading causes of adult disability. Part of the variability in functional outcome after stroke has been attributed to genetic factors but no locus has been consistently associated with stroke outcome. Objective: Our aim was to identify genetic loci influencing the recovery process using accurate phenotyping to produce the largest GWAS (genome-wide association study) in ischemic stroke recovery to date. Methods and Results: A 12-cohort, 2-phase (discovery-replication and joint) meta-analysis of GWAS included anterior-territory and previously independent ischemic stroke cases. Functional outcome was recorded using 3-month modified Rankin Scale. Analyses were adjusted for confounders such as discharge National Institutes of Health Stroke Scale. A gene-based burden test was performed. The discovery phase (n=1225) was followed by open (n=2482) and stringent joint-analyses (n=1791). Those cohorts with modified Rankin Scale recorded at time points other than 3-month or incomplete data on previous functional status were excluded in the stringent analyses. Novel variants in PATJ (Pals1-associated tight junction) gene were associated with worse functional outcome at 3-month after stroke. The top variant was rs76221407 (G allele, β=0.40, P=1.70×10-9). Conclusions: Our results identify a set of common variants in PATJ gene associated with 3-month functional outcome at genome-wide significance level. Future studies should examine the role of PATJ in stroke recovery and consider stringent phenotyping to enrich the information captured to unveil additional stroke outcome loci.
AB - © 2018 American Heart Association, Inc. Rationale: Ischemic stroke is among the leading causes of adult disability. Part of the variability in functional outcome after stroke has been attributed to genetic factors but no locus has been consistently associated with stroke outcome. Objective: Our aim was to identify genetic loci influencing the recovery process using accurate phenotyping to produce the largest GWAS (genome-wide association study) in ischemic stroke recovery to date. Methods and Results: A 12-cohort, 2-phase (discovery-replication and joint) meta-analysis of GWAS included anterior-territory and previously independent ischemic stroke cases. Functional outcome was recorded using 3-month modified Rankin Scale. Analyses were adjusted for confounders such as discharge National Institutes of Health Stroke Scale. A gene-based burden test was performed. The discovery phase (n=1225) was followed by open (n=2482) and stringent joint-analyses (n=1791). Those cohorts with modified Rankin Scale recorded at time points other than 3-month or incomplete data on previous functional status were excluded in the stringent analyses. Novel variants in PATJ (Pals1-associated tight junction) gene were associated with worse functional outcome at 3-month after stroke. The top variant was rs76221407 (G allele, β=0.40, P=1.70×10-9). Conclusions: Our results identify a set of common variants in PATJ gene associated with 3-month functional outcome at genome-wide significance level. Future studies should examine the role of PATJ in stroke recovery and consider stringent phenotyping to enrich the information captured to unveil additional stroke outcome loci.
KW - allele
KW - genetic loci
KW - genetic variant
KW - genome-wide association study
KW - ischemic stroke
KW - Disability Evaluation
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study
KW - Stroke/diagnosis
KW - Gene Frequency
KW - Humans
KW - Risk Factors
KW - Brain Ischemia/diagnosis
KW - Stroke Rehabilitation
KW - Treatment Outcome
KW - Recovery of Function
KW - Tight Junction Proteins/genetics
KW - Phenotype
KW - Polymorphism, Single Nucleotide
KW - GENETICS
KW - SCALE
UR - http://www.mendeley.com/research/patj-low-frequency-variants-associated-worse-ischemic-stroke-functional-outcome-genomewide-metaanaly
U2 - 10.1161/CIRCRESAHA.118.313533
DO - 10.1161/CIRCRESAHA.118.313533
M3 - Article
C2 - 30582445
VL - 124
SP - 114
EP - 120
JO - Circulation Research
JF - Circulation Research
SN - 0009-7330
IS - 1
ER -