Evidence map›Paper›PMID 30661490›Full record

ArticleStroke2019

Genetic Imbalance Is Associated With Functional Outcome After Ischemic Stroke.

Dorothea Pfeiffer, Bowang Chen, Kristina Schlicht, Philip Ginsbach, Sherine Abboud, Anna Bersano, Steve Bevan, Tobias Brandt, Valeria Caso, Stéphanie Debette and 36 more

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

Article in Stroke, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.8field-weighted citation impact, top 10% 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

18 citing papers in PubMed, 38 citations in OpenAlex.

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  12. International stroke genetics consortium recommendations for studies of genetics of stroke outcome and recovery.International journal of stroke : official journal of the International Stroke Society · 2022
    Article
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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

46 authors at 20 institutions in 13 countries.

Dorothea PfeifferFrom the Department of Neurology, Heidelberg University Hospital, Germany (D.P., T.B., E.H., M. Kloss, I.W., C.G.-G.).
Bowang ChenDepartment of Biology, Southern University of Science and Technology, Shenzhen, China (B.C.).
Kristina SchlichtInstitute of Medical Informatics and Statistics, Kiel University, University Hospital Schleswig-Holstein Campus Kiel, Germany (K.S., S.F.-W., M. Krawczak).
Philip GinsbachSchool of Informatics, University of Edinburgh, United Kingdom (P.G.).
Sherine AbboudLaboratory of Experimental Neurology, Université Libre de Bruxelles, Brussels, Belgium (S.A.).
Anna BersanoCerebrovascular Unit IRCCS Foundation C. Besta Neurological Institute, Milan, Italy (A.B.).
Steve BevanSchool of Life Science, University of Lincoln, United Kingdom (S.B.).
Tobias BrandtFrom the Department of Neurology, Heidelberg University Hospital, Germany (D.P., T.B., E.H., M. Kloss, I.W., C.G.-G.).
Valeria CasoStroke Unit, Perugia University Hospital, Italy (V.C.).
Stéphanie DebetteInserm, Bordeaux Population Health Research Center, UMR 1219, University of Bordeaux, France (S.D.).
Philipp ErhartDepartment of Vascular and Endovascular Surgery, University Hospital Heidelberg, Germany (P.E.).
Sandra Freitag-WolfInstitute of Medical Informatics and Statistics, Kiel University, University Hospital Schleswig-Holstein Campus Kiel, Germany (K.S., S.F.-W., M. Krawczak).
Giacomo GiacaloneDepartment of Neurology, San Raffaele University Hospital, Milan, Italy (G.G.).
Armin J GrauDepartment of Neurology, Klinikum Ludwigshafen, Germany (A.J.G.).
Eyad HayaniFrom the Department of Neurology, Heidelberg University Hospital, Germany (D.P., T.B., E.H., M. Kloss, I.W., C.G.-G.).
Christina JernThe Sahlgrenska Academy, University of Gothenburg, Sweden (C.J.).
Jordi Jiménez-CondeIMIM-Parc de Salut Mar, Universitat Autonoma de Barcelona, Spain (J.J.-C.).
Manja KlossFrom the Department of Neurology, Heidelberg University Hospital, Germany (D.P., T.B., E.H., M. Kloss, I.W., C.G.-G.).
Michael KrawczakInstitute of Medical Informatics and Statistics, Kiel University, University Hospital Schleswig-Holstein Campus Kiel, Germany (K.S., S.F.-W., M. Krawczak).
Jin-Moo LeeDepartment of Neurology, Washington University School of Medicine, St Louis, MO (J.-M.L.).
Robin LemmensDepartment of Neurosciences, Experimental Neurology, and Leuven Brain Institute, KU Leuven, University of Leuven, Belgium (R.L.).
Didier LeysDepartment of Neurology, University of Lille, France (D.L.).
Christoph LichyDepartment of Neurology, Klinikum Memmingen, Germany (C.L.).
Jane M MaguireFaculty of Health, University of Technology Sydney, Australia (J.M.M.).
Juan J MartinDepartment of Neurology, Sanatorio Allende, Cordoba, Argentina (J.J.M.).
Antti J MetsoDepartment of Neurology, Helsinki University Central Hospital, Finland (A.J.M., T.M.M., T.T.).
Tiina M MetsoDepartment of Neurology, Helsinki University Central Hospital, Finland (A.J.M., T.M.M., T.T.).
Braxton D MitchellDivision of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore (B.D.M.).
Alessandro PezziniDepartment of Clinical and Experimental Sciences, Neurology Clinic, University of Brescia, Italy (A.P., E.D.Z.).
Jonathan RosandCenter for Genomic Medicine (J.R.), Massachusetts General Hospital, Boston.
Natalia S RostDepartment of Neurology (N.S.R.), Massachusetts General Hospital, Boston.
Martin StenmanDepartment of Clinical Sciences Lund, Neurology, Lund University, Sweden (M.S., A.L.).
Turgut TatlisumakDepartment of Neurology, Helsinki University Central Hospital, Finland (A.J.M., T.M.M., T.T.).
Vincent ThijsStroke Division, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Heidelberg, Victoria, Australia (V.T.).
Emmanuel TouzéParis Descartes University, INSERM UMR S894, Department of Neurology, Sainte-Anne Hospital, Paris, France (E.T.).
Christopher TraenkaDepartment of Neurology and Stroke Center, University Hospital Basel, Switzerland (C.T., S.T.E., P.A.L.).
Inge WernerFrom the Department of Neurology, Heidelberg University Hospital, Germany (D.P., T.B., E.H., M. Kloss, I.W., C.G.-G.).
Daniel WooDepartment of Neurology and Rehabilitation Medicine, University of Cincinnati, OH (D.W.).
Elisabetta Del ZottoDepartment of Clinical and Experimental Sciences, Neurology Clinic, University of Brescia, Italy (A.P., E.D.Z.).
Stefan T EngelterDepartment of Neurology and Stroke Center, University Hospital Basel, Switzerland (C.T., S.T.E., P.A.L.).
Steven J KittnerDepartment of Neurology, Veterans Affairs Medical Center, Baltimore, MD (S.J.K., J.W.C.); and Department of Neurology University of Maryland School of Medicine, Baltimore (S.J.K., J.W.C.).
John W ColeDepartment of Neurology, Veterans Affairs Medical Center, Baltimore, MD (S.J.K., J.W.C.); and Department of Neurology University of Maryland School of Medicine, Baltimore (S.J.K., J.W.C.).
Caspar Grond-GinsbachFrom the Department of Neurology, Heidelberg University Hospital, Germany (D.P., T.B., E.H., M. Kloss, I.W., C.G.-G.).
Philippe A LyrerDepartment of Neurology and Stroke Center, University Hospital Basel, Switzerland (C.T., S.T.E., P.A.L.).
Arne LindgrenDepartment of Clinical Sciences Lund, Neurology, Lund University, Sweden (M.S., A.L.).
CADISP; GISCOME; SiGN studies; and ISGC
Heidelberg University · DEKiel University · DEUniversity Hospital Heidelberg · DEHelsinki University Hospital · FIMassachusetts General Hospital · USUniversity Hospital of Basel · CHUniversity of Brescia · ITUniversity of Gothenburg · SECentre Hospitalier Universitaire de Caen · FRFelix Platter-Hospital · CHFlorey Institute of Neuroscience and Mental Health · AUFondazione IRCCS Istituto Neurologico Carlo Besta · ITFundacion Allende · ARKlinikum Ludwigshafen · DEKU Leuven · BELund University · SEParc de Salut · ESSan Raffaele University of Rome · ITSkåne University Hospital · SESouthern University of Science and Technology · CN

Funding

Research BaseP30DK072488 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI MITCHELL, BRAXTON D, TAYLOR, SIMEON I. · 2005 to 2019
$17.3M
The NINDS International Stroke Genetics Consortium StudyU01NS069208 · NINDS · UNIVERSITY OF MARYLAND BALTIMORE · PI KITTNER, STEVEN J · 2010 to 2013
$9.4M
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
NIDDK NIH HHS P30 DK072488NINDS NIH HHS R01 NS100178NINDS NIH HHS R01 NS105150NINDS NIH HHS U01 NS069208
6 · The paper itself

Abstract

Background and Purpose- We sought to explore the effect of genetic imbalance on functional outcome after ischemic stroke (IS). Methods- Copy number variation was identified in high-density single-nucleotide polymorphism microarray data of IS patients from the CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) and SiGN (Stroke Genetics Network)/GISCOME (Genetics of Ischaemic Stroke Functional Outcome) networks. Genetic imbalance, defined as total number of protein-coding genes affected by copy number variations in an individual, was compared between patients with favorable (modified Rankin Scale score of 0-2) and unfavorable (modified Rankin Scale score of ≥3) outcome after 3 months. Subgroup analyses were confined to patients with imbalance affecting ohnologs-a class of dose-sensitive genes, or to those with imbalance not affecting ohnologs. The association of imbalance with outcome was analyzed by logistic regression analysis, adjusted for age, sex, stroke subtype, stroke severity, and ancestry. Results- The study sample comprised 816 CADISP patients (age 44.2±10.3 years) and 2498 SiGN/GISCOME patients (age 67.7±14.2 years). Outcome was unfavorable in 122 CADISP and 889 SiGN/GISCOME patients. Multivariate logistic regression analysis revealed that increased genetic imbalance was associated with less favorable outcome in both samples (CADISP: P=0.0007; odds ratio=0.89; 95% CI, 0.82-0.95 and SiGN/GISCOME: P=0.0036; odds ratio=0.94; 95% CI, 0.91-0.98). The association was independent of age, sex, stroke severity on admission, stroke subtype, and ancestry. On subgroup analysis, imbalance affecting ohnologs was associated with outcome (CADISP: odds ratio=0.88; 95% CI, 0.80-0.95 and SiGN/GISCOME: odds ratio=0.93; 95% CI, 0.89-0.98) whereas imbalance without ohnologs lacked such an association. Conclusions- Increased genetic imbalance was associated with poorer functional outcome after IS in both study populations. Subgroup analysis revealed that this association was driven by presence of ohnologs in the respective copy number variations, suggesting a causal role of the deleterious effects of genetic imbalance.

Indexed as

Gene DosageAdultAgedBrain IschemiaChromosomes, HumanFollow-Up StudiesGene DuplicationGenotypeHumansMiddle AgedPolymorphism, Single NucleotideRecovery of FunctionSeverity of Illness IndexDNA copy number variationsgeneticspolymorphism, single nucleotideprognosisstroke

Identifiers

PMID30661490
PMCPMC7441497
OpenAlexW2910184695

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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.