Data from: Genome-wide association meta-analysis of functional outcome after ischemic stroke

Objective: To discover common genetic variants associated with post-stroke
outcomes using a genome-wide association (GWA) study. Methods: The study
comprised 6,165 patients with ischemic stroke from 12 studies in Europe,
USA and Australia included in the Genetics of Ischaemic Stroke Functional
Outcome (GISCOME) network. The primary outcome was modified Rankin Scale
(mRS) score after 60-190 days, evaluated as two dichotomous variables (0-2
versus 3-6 and 0-1 versus 2-6) and subsequently as an ordinal variable.
GWA analyses were performed in each study independently and results were
meta-analyzed. Analyses were adjusted for age, sex, stroke severity
(baseline NIH Stroke Scale score), and ancestry. The significance level
was P<5×10-8. Results: We identified one genetic variant associated
with functional outcome with genome-wide significance (mRS 0-2 vs 3-6,
P=6.8×10-9). This intronic variant (rs1842681) in the LOC105372028 gene,
is a previously reported trans-eQTL for PPP1R21, which encodes a
regulatory subunit of protein phosphatase 1 (PP1). This ubiquitous
phosphatase is implicated in brain functions such as brain plasticity.
Several variants discovered in this study demonstrated suggestive
association with outcome (P<10-5), some of which are within or near
genes with experimental evidence of influence on ischemic stroke volume
and/or brain recovery (e.g. NTN4, TEK and PTCH1). Conclusions: In this
large GWA study on functional outcome after ischemic stroke we report one
significant variant and several variants with suggestive association to
outcome three months after stroke onset with plausible mechanistic links
to post-stroke recovery. Future replication studies and exploration of
potential functional mechanisms for identified genetic variants are
warranted.