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

Mola-Caminal, M; Carrera, C; Soriano-Tárraga, C; Giralt-Steinhauer, E; Díaz-Navarro, RM; Tur, S; Jiménez, C; Medina-Dols, A; Cullell, N; Torres-Aguila, NP; Muiño, E; Rodríguez-Campello, A; Ois, A; Cuadrado-Godia, E; Vivanco-Hidalgo, RM; Hernandez-Guillamon, M; Solé, M; Delgado, P; Bustamante, A; García-Berrocoso, T; Mendióroz, M; Castellanos, M; Serena, J; Martí-Fàbregas, J; Segura, T; Serrano-Heras, G; Obach, V; Ribó, M; Molina, CA; Alvarez-Sabín, J; Palomeras, E; Freijo, M; Font, MA; Rosand, J; Rost, NS; Gallego-Fabrega, C; Lee, JM; Heitsch, L; Ibanez, L; Cruchaga, C; Phuah, CL; Lemmens, R; Thijs, V; Lindgren, A; Maguire, J; Rannikmae, K; Sudlow, CL; Jern, C; Stanne, TM; Lorentzen, E; Muñoz-Narbona, L; Dávalos, A; López-Cancio, E; Worrall, BB; Woo, D; Kittner, SJ; Mitchell, BD; Montaner, J; Roquer, J; Krupinski, J; Estivill, X; Rabionet, R; Vives-Bauzá, C; Fernández-Cadenas, I; Jimenez-Conde, J

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

Mola-Caminal, M Carrera, C Soriano-Tárraga, C Giralt-Steinhauer, E Díaz-Navarro, RM Tur, S Jiménez, C Medina-Dols, A Cullell, N Torres-Aguila, NP Muiño, E Rodríguez-Campello, A Ois, A Cuadrado-Godia, E Vivanco-Hidalgo, RM Hernandez-Guillamon, M Solé, M Delgado, P Bustamante, A García-Berrocoso, T Mendióroz, M Castellanos, M Serena, J Martí-Fàbregas, J Segura, T Serrano-Heras, G Obach, V Ribó, M Molina, CA Alvarez-Sabín, J Palomeras, E Freijo, M Font, MA Rosand, J Rost, NS Gallego-Fabrega, C Lee, JM Heitsch, L Ibanez, L Cruchaga, C Phuah, CL Lemmens, R Thijs, V Lindgren, A Maguire, J

Rannikmae, K Sudlow, CL Jern, C Stanne, TM Lorentzen, E Muñoz-Narbona, L Dávalos, A López-Cancio, E Worrall, BB Woo, D Kittner, SJ Mitchell, BD Montaner, J Roquer, J Krupinski, J Estivill, X Rabionet, R Vives-Bauzá, C Fernández-Cadenas, I Jimenez-Conde, J

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Publication Type:: Journal Article
Citation:: Circulation Research, 2019, 124 (1), pp. 114 - 120
Issue Date:: 2019-01-04

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Field	Value	Language
dc.contributor.author	Mola-Caminal, M	en_US
dc.contributor.author	Carrera, C	en_US
dc.contributor.author	Soriano-Tárraga, C	en_US
dc.contributor.author	Giralt-Steinhauer, E	en_US
dc.contributor.author	Díaz-Navarro, RM	en_US
dc.contributor.author	Tur, S	en_US
dc.contributor.author	Jiménez, C	en_US
dc.contributor.author	Medina-Dols, A	en_US
dc.contributor.author	Cullell, N	en_US
dc.contributor.author	Torres-Aguila, NP	en_US
dc.contributor.author	Muiño, E	en_US
dc.contributor.author	Rodríguez-Campello, A	en_US
dc.contributor.author	Ois, A	en_US
dc.contributor.author	Cuadrado-Godia, E	en_US
dc.contributor.author	Vivanco-Hidalgo, RM	en_US
dc.contributor.author	Hernandez-Guillamon, M	en_US
dc.contributor.author	Solé, M	en_US
dc.contributor.author	Delgado, P	en_US
dc.contributor.author	Bustamante, A	en_US
dc.contributor.author	García-Berrocoso, T	en_US
dc.contributor.author	Mendióroz, M	en_US
dc.contributor.author	Castellanos, M	en_US
dc.contributor.author	Serena, J	en_US
dc.contributor.author	Martí-Fàbregas, J	en_US
dc.contributor.author	Segura, T	en_US
dc.contributor.author	Serrano-Heras, G	en_US
dc.contributor.author	Obach, V	en_US
dc.contributor.author	Ribó, M	en_US
dc.contributor.author	Molina, CA	en_US
dc.contributor.author	Alvarez-Sabín, J	en_US
dc.contributor.author	Palomeras, E	en_US
dc.contributor.author	Freijo, M	en_US
dc.contributor.author	Font, MA	en_US
dc.contributor.author	Rosand, J	en_US
dc.contributor.author	Rost, NS	en_US
dc.contributor.author	Gallego-Fabrega, C	en_US
dc.contributor.author	Lee, JM	en_US
dc.contributor.author	Heitsch, L	en_US
dc.contributor.author	Ibanez, L	en_US
dc.contributor.author	Cruchaga, C	en_US
dc.contributor.author	Phuah, CL	en_US
dc.contributor.author	Lemmens, R	en_US
dc.contributor.author	Thijs, V	en_US
dc.contributor.author	Lindgren, A	en_US
dc.contributor.author	Maguire, J https://orcid.org/0000-0001-5722-8311	en_US
dc.contributor.author	Rannikmae, K	en_US
dc.contributor.author	Sudlow, CL	en_US
dc.contributor.author	Jern, C	en_US
dc.contributor.author	Stanne, TM	en_US
dc.contributor.author	Lorentzen, E	en_US
dc.contributor.author	Muñoz-Narbona, L	en_US
dc.contributor.author	Dávalos, A	en_US
dc.contributor.author	López-Cancio, E	en_US
dc.contributor.author	Worrall, BB	en_US
dc.contributor.author	Woo, D	en_US
dc.contributor.author	Kittner, SJ	en_US
dc.contributor.author	Mitchell, BD	en_US
dc.contributor.author	Montaner, J	en_US
dc.contributor.author	Roquer, J	en_US
dc.contributor.author	Krupinski, J	en_US
dc.contributor.author	Estivill, X	en_US
dc.contributor.author	Rabionet, R	en_US
dc.contributor.author	Vives-Bauzá, C	en_US
dc.contributor.author	Fernández-Cadenas, I	en_US
dc.contributor.author	Jimenez-Conde, J	en_US
dc.date.issued	2019-01-04	en_US
dc.identifier.citation	Circulation Research, 2019, 124 (1), pp. 114 - 120	en_US
dc.identifier.issn	0009-7330	en_US
dc.identifier.uri	http://hdl.handle.net/10453/135649
dc.description.abstract	© 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.	en_US
dc.relation.ispartof	Circulation Research	en_US
dc.relation.isbasedon	10.1161/CIRCRESAHA.118.313533	en_US
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject.classification	Cardiovascular System & Hematology	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Brain Ischemia	en_US
dc.subject.mesh	Genetic Predisposition to Disease	en_US
dc.subject.mesh	Disability Evaluation	en_US
dc.subject.mesh	Treatment Outcome	en_US
dc.subject.mesh	Risk Factors	en_US
dc.subject.mesh	Recovery of Function	en_US
dc.subject.mesh	Gene Frequency	en_US
dc.subject.mesh	Phenotype	en_US
dc.subject.mesh	Polymorphism, Single Nucleotide	en_US
dc.subject.mesh	Stroke	en_US
dc.subject.mesh	Genome-Wide Association Study	en_US
dc.subject.mesh	Tight Junction Proteins	en_US
dc.subject.mesh	Stroke Rehabilitation	en_US
dc.title	PATJ Low Frequency Variants Are Associated with Worse Ischemic Stroke Functional Outcome: A Genome-Wide Meta-Analysis	en_US
dc.type	Journal Article
utslib.citation.volume	1	en_US
utslib.citation.volume	124	en_US
utslib.for	1102 Cardiorespiratory Medicine and Haematology	en_US
utslib.for	1103 Clinical Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Health
pubs.organisational-group	/University of Technology Sydney/Faculty of Health/Nursing
utslib.copyright.status	closed_access	*
pubs.issue	1	en_US
pubs.publication-status	Published	en_US
pubs.volume	124	en_US

Abstract:

© 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.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/135649