Genome-wide association meta-analysis of functional outcome after ischemic stroke.

Neurology
Martin SöderholmInternational Stroke Genetics Consortium, the NINDS-SiGN Consortium, and the Genetics of Ischaemic Stroke Functional Outcome

Abstract

To discover common genetic variants associated with poststroke outcomes using a genome-wide association (GWA) study. The study comprised 6,165 patients with ischemic stroke from 12 studies in Europe, the United States, and Australia included in the GISCOME (Genetics of Ischaemic Stroke Functional Outcome) network. The primary outcome was modified Rankin Scale score after 60 to 190 days, evaluated as 2 dichotomous variables (0-2 vs 3-6 and 0-1 vs 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. We identified one genetic variant associated with functional outcome with genome-wide significance (modified Rankin Scale scores 0-2 vs 3-6, p = 5.3 × 10-9). This intronic variant (rs1842681) in the LOC105372028 gene is a previously reported trans-expression quantitative trait locus for PPP1R21, which encodes a regulatory subunit of protein phosphatase 1. This ubiquitous phosphatase is implicated in brain functions such as brain plasticity. Several variants detected in this study demonstrated suggestive association...Continue Reading

Associated Datasets

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Citations

Oct 9, 2019·Journal of Stroke·Nuria P Torres-AguilaUNKNOWN Acute Endophenotypes Group of the International Stroke Genetics Consortium (ISGC)
Oct 18, 2019·Neurology·Cecilia LaggingUNKNOWN Genetics of Ischaemic Stroke Functional Outcome (GISCOME) network and the International Stroke Genetics Consortium
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Feb 23, 2020·Stroke; a Journal of Cerebral Circulation·James F Meschia
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Methods Mentioned

BETA
PLAA

Software Mentioned

METAL
MATLAB Statistics and Machine Learning Toolbox
PLINK
HaploReg
MATLAB mnrfit
Dryad
GISCOME

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