PATJ Low Frequency Variants Are Associated with Worse Ischemic Stroke Functional Outcome: A Genome-Wide Meta-Analysis
PublisherLippincott Williams and Wilkins
MetadataShow full item record
AbstractRationale: 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.
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85059496757&doi=10.1161%2fCIRCRESAHA.118.313533&partnerID=40&md5=7afd86679ee63f8d790ed1318647e9f1; http://hdl.handle.net/10713/10712
- Loci associated with ischaemic stroke and its subtypes (SiGN): a genome-wide association study.
- Authors: NINDS Stroke Genetics Network (SiGN)., International Stroke Genetics Consortium (ISGC).
- Issue date: 2016 Feb
- Genome-wide association meta-analysis of functional outcome after ischemic stroke.
- Authors: Söderholm M, Pedersen A, Lorentzen E, Stanne TM, Bevan S, Olsson M, Cole JW, Fernandez-Cadenas I, Hankey GJ, Jimenez-Conde J, Jood K, Lee JM, Lemmens R, Levi C, Mitchell BD, Norrving B, Rannikmäe K, Rost NS, Rosand J, Rothwell PM, Scott R, Strbian D, Sturm JW, Sudlow C, Traylor M, Thijs V, Tatlisumak T, Woo D, Worrall BB, Maguire JM, Lindgren A, Jern C, International Stroke Genetics Consortium, the NINDS-SiGN Consortium, and the Genetics of Ischaemic Stroke Functional Outcome (GISCOME) Network.
- Issue date: 2019 Mar 19
- Impact of COX-2 rs5275 and rs20417 and GPIIIa rs5918 polymorphisms on 90-day ischemic stroke functional outcome: a novel finding.
- Authors: Maguire J, Thakkinstian A, Levi C, Lincz L, Bisset L, Sturm J, Scott R, Whyte S, Attia J
- Issue date: 2011 Mar-Apr
- Major Adipokines and the -420C>G Resistin Gene Polymorphism as Predictors of Acute Ischemic Stroke Severity and In-Hospital Outcome.
- Authors: Bouziana SD, Tziomalos K, Goulas A, Vyzantiadis TA, Panderi A, Ηatzitolios AΙ
- Issue date: 2018 Apr
- Shared genetic susceptibility to ischemic stroke and coronary artery disease: a genome-wide analysis of common variants.
- Authors: Dichgans M, Malik R, König IR, Rosand J, Clarke R, Gretarsdottir S, Thorleifsson G, Mitchell BD, Assimes TL, Levi C, O'Donnell CJ, Fornage M, Thorsteinsdottir U, Psaty BM, Hengstenberg C, Seshadri S, Erdmann J, Bis JC, Peters A, Boncoraglio GB, März W, Meschia JF, Kathiresan S, Ikram MA, McPherson R, Stefansson K, Sudlow C, Reilly MP, Thompson JR, Sharma P, Hopewell JC, Chambers JC, Watkins H, Rothwell PM, Roberts R, Markus HS, Samani NJ, Farrall M, Schunkert H, METASTROKE Consortium., CARDIoGRAM Consortium., C4D Consortium., International Stroke Genetics Consortium.
- Issue date: 2014 Jan