PATJ Low Frequency Variants Are Associated With Worse Ischemic Stroke Functional Outcome.

2019-01-04

Mola-Caminal, Marina

Carrera, Caty

Soriano-Tárraga, Carolina

Giralt-Steinhauer, Eva

Díaz-Navarro, Rosa M

Tur, Sílvia

Jiménez, Carmen

Medina-Dols, Aina

Cullell, Natàlia

Torres-Aguila, Nuria P

Muiño, Elena

Rodríguez-Campello, Ana

Ois, Angel

Cuadrado-Godia, Elisa

Vivanco-Hidalgo, Rosa M

Hernandez-Guillamon, Mar

Solé, Montse

Delgado, Pilar

Bustamante, Alejandro

García-Berrocoso, Teresa

Mendióroz, Maite

Castellanos, Mar

Serena, Joaquín

Martí-Fàbregas, Joan

Segura, Tomás

Serrano-Heras, Gemma

Obach, Victor

Ribó, Marc

Molina, Carlos A

Alvarez-Sabín, José

Palomeras, Ernest

Freijo, Mar

Font, Maria A

Rosand, Jonathan

Rost, Natalia S

Gallego-Fabrega, Cristina

Lee, Jin-Moo

Heitsch, Laura

Ibanez, Laura

Cruchaga, Carlos

Phuah, Chia-Ling

Lemmens, Robin

Thijs, Vincent N

Lindgren, Arne

Maguire, Jane

Rannikmae, Kristiina

Sudlow, Catherine L

Jern, Christina

Stanne, Tara M

Lorentzen, Erik

Muñoz-Narbona, Lucía

Dávalos, Antonio

López-Cancio, Elena

Worrall, Bradford B

Woo, Daniel

Kittner, Steven J

Mitchell, Braxton D

Montaner, Joan

Roquer, Jaume

Krupinski, Jurek

Estivill, Xavier

Rabionet, Raquel

Vives-Bauzá, Cristòfol

Fernández-Cadenas, Israel

Jiménez-Conde, Jordi

allele

genetic loci

genetic variant

genome-wide association study

ischemic Stroke

Journal Article

0000-0002-6614-8417

10.1161/CIRCRESAHA.118.313533

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. 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. 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). 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.

link

Circulation research 2019; 124(1): 114-120

Circulation research