PATJ Low Frequency Variants Are Associated with Worse Ischemic Stroke Functional Outcome: A Genome-Wide Meta-Analysis

Marina Mola-Caminal, Caty Carrera, Carolina Soriano-Tárraga, Eva Giralt-Steinhauer, Rosa M. Díaz-Navarro, Sílvia Tur, Carmen Jiménez, Aina Medina-Dols, Natàlia Cullell, Nuria P. Torres-Aguila, Elena Muiño, Ana Rodríguez-Campello, Angel Ois, Elisa Cuadrado-Godia, Rosa M. Vivanco-Hidalgo, Mar Hernandez-Guillamon, Montse Solé, Pilar Delgado, Alejandro Bustamante, Teresa García-BerrocosoMaite Mendióroz, Mar Castellanos, Joaquín Serena, Joan Martí-Fàbregas, Tomás Segura, Gemma Serrano-Heras, Victor Obach, Marc Ribó, Carlos A. Molina, José Alvarez-Sabín, Ernest Palomeras, Mar Freijo, Maria A. Font, Jonathan Rosand, Natalia S. Rost, Cristina Gallego-Fabrega, Jin Moo Lee, Laura Heitsch, Laura Ibanez, Carlos Cruchaga, Chia Ling Phuah, Robin Lemmens, Vincent Thijs, Arne Lindgren, Jane Maguire, Kristiina Rannikmae, Catherine L. Sudlow, Christina Jern, Tara M. Stanne, Erik Lorentzen, Lucía Muñoz-Narbona, Antonio Dávalos, Elena López-Cancio, Bradford B. Worrall, Daniel Woo, Steven J. Kittner, Braxton D. Mitchell, Joan Montaner, Jaume Roquer, Jurek Krupinski, Xavier Estivill, Raquel Rabionet, Cristòfol Vives-Bauzá, Israel Fernández-Cadenas, Jordi Jimenez-Conde

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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.

Original languageEnglish
Pages (from-to)114-120
Number of pages7
JournalCirculation research
Issue number1
StatePublished - Jan 4 2019


  • allele
  • genetic loci
  • genetic variant
  • genome-wide association study
  • ischemic stroke


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