Evidence map›Paper›PMID 38181310›Full record

ArticleNeurology2024

Genome-Wide Association Studies of 3 Distinct Recovery Phenotypes in Mild Ischemic Stroke.

Chad M Aldridge, Robynne Braun, Keith Lohse, Adam de Havenon, John W Cole, Steven C Cramer, Arne G Lindgren, Keith L Keene, Fang-Chi Hsu, Bradford B Worrall

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
3.3field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 7 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Chad M AldridgeFrom the Department of Neurology (C.M.A., B.B.W.), University of Virginia, Charlottesville; Department of Neurology (R.B., J.W.C.), University of Maryland, Baltimore; Program in Physical Therapy (K.L.), Washington University; Department of Neurology (K.L.), Washington University, St. Louis, MO; Department of Neurology (A.H.), Center for Brain and Mind Health, Yale University, New Haven, CT; Department of Neurology (S.C.C.), University of California Los Angeles; California Rehabilitation Institute (S.C.C.), Los Angeles; Department of Clinical Sciences Lund, Neurology (A.G.L.), Lund University; Department of Neurology (A.G.L.), Skane University Hospital, Sweden; Department of Public Health Sciences (K.L.K., B.B.W.); Center for Health Equity and Precision Public Health (K.L.K.), University of Virginia, Charlottesville; and Department of Biostatistics (F.-C.H.), School of Medicine, Wake Forest University, Winston-Salem, NC.ORCID 0000-0003-0539-9762
Robynne BraunFrom the Department of Neurology (C.M.A., B.B.W.), University of Virginia, Charlottesville; Department of Neurology (R.B., J.W.C.), University of Maryland, Baltimore; Program in Physical Therapy (K.L.), Washington University; Department of Neurology (K.L.), Washington University, St. Louis, MO; Department of Neurology (A.H.), Center for Brain and Mind Health, Yale University, New Haven, CT; Department of Neurology (S.C.C.), University of California Los Angeles; California Rehabilitation Institute (S.C.C.), Los Angeles; Department of Clinical Sciences Lund, Neurology (A.G.L.), Lund University; Department of Neurology (A.G.L.), Skane University Hospital, Sweden; Department of Public Health Sciences (K.L.K., B.B.W.); Center for Health Equity and Precision Public Health (K.L.K.), University of Virginia, Charlottesville; and Department of Biostatistics (F.-C.H.), School of Medicine, Wake Forest University, Winston-Salem, NC.ORCID 0000-0002-3579-6665
Keith LohseFrom the Department of Neurology (C.M.A., B.B.W.), University of Virginia, Charlottesville; Department of Neurology (R.B., J.W.C.), University of Maryland, Baltimore; Program in Physical Therapy (K.L.), Washington University; Department of Neurology (K.L.), Washington University, St. Louis, MO; Department of Neurology (A.H.), Center for Brain and Mind Health, Yale University, New Haven, CT; Department of Neurology (S.C.C.), University of California Los Angeles; California Rehabilitation Institute (S.C.C.), Los Angeles; Department of Clinical Sciences Lund, Neurology (A.G.L.), Lund University; Department of Neurology (A.G.L.), Skane University Hospital, Sweden; Department of Public Health Sciences (K.L.K., B.B.W.); Center for Health Equity and Precision Public Health (K.L.K.), University of Virginia, Charlottesville; and Department of Biostatistics (F.-C.H.), School of Medicine, Wake Forest University, Winston-Salem, NC.ORCID 0000-0002-7643-3887
Adam de HavenonFrom the Department of Neurology (C.M.A., B.B.W.), University of Virginia, Charlottesville; Department of Neurology (R.B., J.W.C.), University of Maryland, Baltimore; Program in Physical Therapy (K.L.), Washington University; Department of Neurology (K.L.), Washington University, St. Louis, MO; Department of Neurology (A.H.), Center for Brain and Mind Health, Yale University, New Haven, CT; Department of Neurology (S.C.C.), University of California Los Angeles; California Rehabilitation Institute (S.C.C.), Los Angeles; Department of Clinical Sciences Lund, Neurology (A.G.L.), Lund University; Department of Neurology (A.G.L.), Skane University Hospital, Sweden; Department of Public Health Sciences (K.L.K., B.B.W.); Center for Health Equity and Precision Public Health (K.L.K.), University of Virginia, Charlottesville; and Department of Biostatistics (F.-C.H.), School of Medicine, Wake Forest University, Winston-Salem, NC.ORCID 0000-0001-8178-8597
John W ColeFrom the Department of Neurology (C.M.A., B.B.W.), University of Virginia, Charlottesville; Department of Neurology (R.B., J.W.C.), University of Maryland, Baltimore; Program in Physical Therapy (K.L.), Washington University; Department of Neurology (K.L.), Washington University, St. Louis, MO; Department of Neurology (A.H.), Center for Brain and Mind Health, Yale University, New Haven, CT; Department of Neurology (S.C.C.), University of California Los Angeles; California Rehabilitation Institute (S.C.C.), Los Angeles; Department of Clinical Sciences Lund, Neurology (A.G.L.), Lund University; Department of Neurology (A.G.L.), Skane University Hospital, Sweden; Department of Public Health Sciences (K.L.K., B.B.W.); Center for Health Equity and Precision Public Health (K.L.K.), University of Virginia, Charlottesville; and Department of Biostatistics (F.-C.H.), School of Medicine, Wake Forest University, Winston-Salem, NC.ORCID 0000-0001-9263-8930
Steven C CramerFrom the Department of Neurology (C.M.A., B.B.W.), University of Virginia, Charlottesville; Department of Neurology (R.B., J.W.C.), University of Maryland, Baltimore; Program in Physical Therapy (K.L.), Washington University; Department of Neurology (K.L.), Washington University, St. Louis, MO; Department of Neurology (A.H.), Center for Brain and Mind Health, Yale University, New Haven, CT; Department of Neurology (S.C.C.), University of California Los Angeles; California Rehabilitation Institute (S.C.C.), Los Angeles; Department of Clinical Sciences Lund, Neurology (A.G.L.), Lund University; Department of Neurology (A.G.L.), Skane University Hospital, Sweden; Department of Public Health Sciences (K.L.K., B.B.W.); Center for Health Equity and Precision Public Health (K.L.K.), University of Virginia, Charlottesville; and Department of Biostatistics (F.-C.H.), School of Medicine, Wake Forest University, Winston-Salem, NC.ORCID 0000-0002-6214-6211
Arne G LindgrenFrom the Department of Neurology (C.M.A., B.B.W.), University of Virginia, Charlottesville; Department of Neurology (R.B., J.W.C.), University of Maryland, Baltimore; Program in Physical Therapy (K.L.), Washington University; Department of Neurology (K.L.), Washington University, St. Louis, MO; Department of Neurology (A.H.), Center for Brain and Mind Health, Yale University, New Haven, CT; Department of Neurology (S.C.C.), University of California Los Angeles; California Rehabilitation Institute (S.C.C.), Los Angeles; Department of Clinical Sciences Lund, Neurology (A.G.L.), Lund University; Department of Neurology (A.G.L.), Skane University Hospital, Sweden; Department of Public Health Sciences (K.L.K., B.B.W.); Center for Health Equity and Precision Public Health (K.L.K.), University of Virginia, Charlottesville; and Department of Biostatistics (F.-C.H.), School of Medicine, Wake Forest University, Winston-Salem, NC.ORCID 0000-0003-1942-7330
Keith L KeeneFrom the Department of Neurology (C.M.A., B.B.W.), University of Virginia, Charlottesville; Department of Neurology (R.B., J.W.C.), University of Maryland, Baltimore; Program in Physical Therapy (K.L.), Washington University; Department of Neurology (K.L.), Washington University, St. Louis, MO; Department of Neurology (A.H.), Center for Brain and Mind Health, Yale University, New Haven, CT; Department of Neurology (S.C.C.), University of California Los Angeles; California Rehabilitation Institute (S.C.C.), Los Angeles; Department of Clinical Sciences Lund, Neurology (A.G.L.), Lund University; Department of Neurology (A.G.L.), Skane University Hospital, Sweden; Department of Public Health Sciences (K.L.K., B.B.W.); Center for Health Equity and Precision Public Health (K.L.K.), University of Virginia, Charlottesville; and Department of Biostatistics (F.-C.H.), School of Medicine, Wake Forest University, Winston-Salem, NC.ORCID 0000-0002-7826-399X
Fang-Chi HsuFrom the Department of Neurology (C.M.A., B.B.W.), University of Virginia, Charlottesville; Department of Neurology (R.B., J.W.C.), University of Maryland, Baltimore; Program in Physical Therapy (K.L.), Washington University; Department of Neurology (K.L.), Washington University, St. Louis, MO; Department of Neurology (A.H.), Center for Brain and Mind Health, Yale University, New Haven, CT; Department of Neurology (S.C.C.), University of California Los Angeles; California Rehabilitation Institute (S.C.C.), Los Angeles; Department of Clinical Sciences Lund, Neurology (A.G.L.), Lund University; Department of Neurology (A.G.L.), Skane University Hospital, Sweden; Department of Public Health Sciences (K.L.K., B.B.W.); Center for Health Equity and Precision Public Health (K.L.K.), University of Virginia, Charlottesville; and Department of Biostatistics (F.-C.H.), School of Medicine, Wake Forest University, Winston-Salem, NC.ORCID 0000-0002-3310-184X
Bradford B WorrallFrom the Department of Neurology (C.M.A., B.B.W.), University of Virginia, Charlottesville; Department of Neurology (R.B., J.W.C.), University of Maryland, Baltimore; Program in Physical Therapy (K.L.), Washington University; Department of Neurology (K.L.), Washington University, St. Louis, MO; Department of Neurology (A.H.), Center for Brain and Mind Health, Yale University, New Haven, CT; Department of Neurology (S.C.C.), University of California Los Angeles; California Rehabilitation Institute (S.C.C.), Los Angeles; Department of Clinical Sciences Lund, Neurology (A.G.L.), Lund University; Department of Neurology (A.G.L.), Skane University Hospital, Sweden; Department of Public Health Sciences (K.L.K., B.B.W.); Center for Health Equity and Precision Public Health (K.L.K.), University of Virginia, Charlottesville; and Department of Biostatistics (F.-C.H.), School of Medicine, Wake Forest University, Winston-Salem, NC.ORCID 0000-0001-9386-4091
University of Maryland, Baltimore · US

Funding

Vitamin Intervention for Stroke Prevention (VISP)R01NS034447 · NINDS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI TOOLE, JAMES F · 1996 to 2006
$18.0M
Healthy Aging Neighborhoods of Diversity Across LifespanZ01AG000513 · NIA · NATIONAL INSTITUTE ON AGING · PI EVANS, MICHELE K · 2001 to 2008
$6.8M
Genetics of ischemic stroke in the SiGN ConsortiumR01NS100178 · NINDS · UNIVERSITY OF MARYLAND BALTIMORE · PI KITTNER, STEVEN J, MITCHELL, BRAXTON D · 2017 to 2021
$3.0M
Genetics of Early-Onset Ischemic Stroke ConsortiumR01NS105150 · NINDS · UNIVERSITY OF MARYLAND BALTIMORE · PI KITTNER, STEVEN J, MITCHELL, BRAXTON D · 2018 to 2022
$3.0M
CNV And Stroke (CaNVAS)R01NS114045 · NINDS · UNIVERSITY OF MARYLAND BALTIMORE · PI COLE, JOHN W. · 2020 to 2024
$2.6M
Randomized Clinical Trials - Whole Genome Studies Coordinating CenterU01HG005157 · NHGRI · UNIVERSITY OF WASHINGTON · PI HEAGERTY, PATRICK J, WEIR, BRUCE S. · 2009 to 2011
$2.4M
Pharmacogenomic studies in VISP: results & implications for clinical trial designU01HG005160 · NHGRI · UNIVERSITY OF VIRGINIA · PI SALE, MICHELE M, WORRALL, BRADFORD B · 2009 to 2011
$1.9M
Intramural NIH HHS Z01 AG000513NHGRI NIH HHS U01 HG005157NHGRI NIH HHS U01 HG005160NINDS NIH HHS R01 NS034447NINDS NIH HHS R01 NS100178NINDS NIH HHS R01 NS105150NINDS NIH HHS R01 NS114045
6 · The paper itself

Abstract

BACKGROUND AND

objectivesStroke genetic research has made substantial progress in the past decade. Its recovery application, however, remains behind, in part due to its reliance on the modified Rankin Scale (mRS) score as a measure of poststroke outcome. The mRS does not map well to biological processes because numerous psychosocial factors drive much of what the mRS captures. Second, the mRS contains multiple disparate biological events into a single measure further limiting its use for biological discovery. This led us to investigate the effect of distinct stroke recovery phenotypes on genetic variation associations with Genome-Wide Association Studies (GWASs) by repurposing the NIH Stroke Scale (NIHSS) and its subscores.

methodsIn the Vitamin Intervention for Stroke Prevention cohort, we estimated changes in cognition, motor, and global impairments over 2 years using specific measures. We included genotyped participants with a total NIHSS score greater than zero at randomization and excluded those with recurrent stroke during the trial. A GWAS linear mixed-effects model predicted score changes, with participant as a random effect, and included initial score, age, sex, treatment group, and the first 5 ancestry principal components.

resultsIn total, 1,270 participants (64% male) were included with a median NIHSS score of 2 (interquartile range [IQR] 1-3) and median age 68 (IQR 59-75) years. At randomization, 20% had cognitive deficits (NIHSS Cog-4 score >0) and 70% had ≥1 motor deficits (impairment score >1). At 2 years, these percentages improved to 7.2% with cognitive deficits and 30% with motor deficits. GWAS identified novel suggestive gene-impairment associations ( DISCUSSION: Defining domain-specific stroke recovery phenotypes and using longitudinal clinical trial designs can help detect novel genes associated with chronic recovery. These data support the use of granular endpoints to identify genetic associations related to stroke recovery.

Indexed as

Ischemic StrokeStrokeAgedATP-Binding Cassette TransportersFemaleGenome-Wide Association StudyHumansJumonji Domain-Containing Histone DemethylasesMaleNerve Tissue ProteinsPhenotypeReceptors, ImmunologicACBD6 protein, humanATP-Binding Cassette TransportersJumonji Domain-Containing Histone DemethylasesKDM4B protein, humanNerve Tissue ProteinsReceptors, Immunologic

Identifiers

PMID38181310
PMCPMC11023036
OpenAlexW4390629274

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.