DOI: 10.5061/dryad.s38kf65
title: Data from: Genome-wide association meta-analysis of functional outcome after ischemic stroke

description: 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&lt;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&lt;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.
description: Supplemental Methods,
 Tables and FiguresSupplemental Methods
 Tables e-1 – e-11 • Table e-1 Study sites, genotyping arrays and cohort
 abbreviations • Table e-2 Characteristics of study population and included
 number of cases by study site • Table e-3 Number of principal components
 included in analyses by study cohort • Table e-4 Genomic inflation factors
 (λ) by each cohort • Table e-5 Top 10 independent loci for mRS 0-2 vs 3-6
 • Table e-6 Top 10 independent loci for ordinal mRS Table e-7 Top 10
 independent loci for mRS 0-2 vs 3-6 (without severity adjustment) • Table
 e-8 Top 10 independent loci for ordinal mRS (without severity adjustment)
 • Table e-9 Top 10 findings for gene-based analysis • Table e-10 Top 5
 loci for mRS 0-2 vs 3-6 in lacunar stroke • Table e-11 Top 5 loci for mRS
 0-2 vs 3-6 in non-lacunar stroke • Table e-12 Top 10 independent loci for
 mRS 0-1 vs 2-6 • Table e-13 Top 10 independnet loci for mRS 0-1 vs 2-6
 (without severity adjustment) Figures e-1 – e-8 • Figure e-1 QQ-plot mRS
 0-2 vs 3-6 (without severity adjustment) • Figure e-2 QQ-plot ordinal mRS
 (without severity adjustment) • Figure e-3 Manhattan and QQ-plots mRS 0-1
 vs 2-6 • Figure e-4 QQ-plot mRS 0-1 vs 2-6 (without severity adjustment) •
 Figure e-5 Minor allele frequency of rs1842681 stratified by mRS score •
 Figure e-6 Manhattan plot mRS 0-2 vs 3-6 (without severity adjustment) •
 Figure e-7 Manhattan plot ordinal mRS (without severity adjustment) •
 Figure e-8 Manhattan plot mRS 0-1 vs 2-6 (without severity
 adjustment)Söderholm et al, supplemental
 material.docx