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

Mola-Caminal, Marina ; Lindgren, Arne LU ; Fernandez-Cadenas, Israel; Jimenez-Conde, Jordi and , (2019) In Circulation Research 124(1). p.114-120
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
allele, genetic loci, genetic variant, genome-wide association study, ischemic stroke
in
Circulation Research
volume
124
issue
1
pages
7 pages
publisher
American Heart Association
external identifiers
  • scopus:85059496757
ISSN
0009-7330
DOI
10.1161/CIRCRESAHA.118.313533
language
English
LU publication?
yes
id
a6664383-aed0-44a8-8689-72978a4c8d27
date added to LUP
2019-01-18 12:45:51
date last changed
2019-05-05 04:49:48
@article{a6664383-aed0-44a8-8689-72978a4c8d27,
  abstract     = {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.},
  author       = {Mola-Caminal, Marina  and Lindgren, Arne and Fernandez-Cadenas, Israel and Jimenez-Conde, Jordi and , },
  issn         = {0009-7330},
  keyword      = {allele,genetic loci,genetic variant,genome-wide association study,ischemic stroke},
  language     = {eng},
  number       = {1},
  pages        = {114--120},
  publisher    = {American Heart Association},
  series       = {Circulation Research},
  title        = {PATJ Low Frequency Variants Are Associated With Worse Ischemic Stroke Functional Outcome},
  url          = {http://dx.doi.org/10.1161/CIRCRESAHA.118.313533},
  volume       = {124},
  year         = {2019},
}