ArticlemedRxiv : the preprint server for health sciences2020
Multi-ancestry genetic study in 5,876 patients identifies an association between excitotoxic genes and early outcomes after acute ischemic stroke.
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Article in medRxiv : the preprint server for health sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2citing papers in PubMed
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2 citing papers in PubMed, 11 citations in OpenAlex.
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Authors and funding
73 authors at 20 institutions in 11 countries.
Laura IbanezDepartment of Psychiatry, Washington University School of Medicine, 660 S. Euclid Avenue, Saint Louis (63110), Missouri, US.
Laura HeitschDepartment of Neurology, Washington University School of Medicine, 660 S. Euclid Avenue; Campus Box 8111; Saint Louis (63110), Missouri, US.
Caty CarreraStroke Unit, Vall d'Hebron University Hospital, Universitat de Barcelona, Passeig de la Vall d'Hebron, 1198; Barcelona (08035), Spain.
Fabiana H G FariasDepartment of Psychiatry, Washington University School of Medicine, 660 S. Euclid Avenue, Saint Louis (63110), Missouri, US.
Rajat DharDepartment of Neurology, Washington University School of Medicine, 660 S. Euclid Avenue; Campus Box 8111; Saint Louis (63110), Missouri, US.
John BuddeDepartment of Psychiatry, Washington University School of Medicine, 660 S. Euclid Avenue, Saint Louis (63110), Missouri, US.
Kristy BergmannDepartment of Psychiatry, Washington University School of Medicine, 660 S. Euclid Avenue, Saint Louis (63110), Missouri, US.
Joseph BradleyDepartment of Psychiatry, Washington University School of Medicine, 660 S. Euclid Avenue, Saint Louis (63110), Missouri, US.
Oscar HarariDepartment of Psychiatry, Washington University School of Medicine, 660 S. Euclid Avenue, Saint Louis (63110), Missouri, US.
Chia-Ling PhuahDepartment of Neurology, Washington University School of Medicine, 660 S. Euclid Avenue; Campus Box 8111; Saint Louis (63110), Missouri, US.
Robin LemmensDepartment of Neuroscience, Katholieke Universiteit Leuven, Campus Gasthuisberg O&N2; Herestraat 49 box 1021; Leuven (BE-3000), Belgium.
Alessandro A Viana Oliveira SouzaDepartment of Neurology, School of Medical Sciences, University of Campinas (UNICAMP), R. Tessalia Viera de Camargo, 126; Cidade Universitaria, Campinas (13083-887), Brazil.
Francisco MonicheDepartment of neurology, Hospital Virgen del Rocio, University of Seville, Avenida Manuel Siurot, s/n; Seville (41013), Spain.
Antonio Cabezas-JuanDepartment of neurology, Hospital Virgen del Rocio, University of Seville, Avenida Manuel Siurot, s/n; Seville (41013), Spain.
Juan Francisco ArenillasDepartment of Neurology, Hospital Clinico Universitario Valladolid, Valladolid University, Avenida Ramon y Cajal, 3; Valladolid (47003), Spain.
Jerzy KrupinksiDepartment of Neurology, Mutua Terrassa University Hospital, Universitat de Barcelona, Plaça del Dr. Robert, 5; Terrassa (08221), Spain.
Natalia CullellFundacio Docencia i Recerca Mutua Terrassa, Universitat de Barcelona, Carrer Sant Antoni, 19; Terrassa (08221), Spain.
Nuria Torres-AguilaFundacio Docencia i Recerca Mutua Terrassa, Universitat de Barcelona, Carrer Sant Antoni, 19; Terrassa (08221), Spain.
Elena MuiñoDepartment of Neurology, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Carrer de Sant Quinti, 89; Barcelona (08041), Spain.
Jara Cárcel-MárquezDepartment of Neurology, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Carrer de Sant Quinti, 89; Barcelona (08041), Spain.
Joan Marti-FabregasDepartment of Neurology, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Carrer de Sant Quinti, 89; Barcelona (08041), Spain.
Raquel Delgado-MederosDepartment of Neurology, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Carrer de Sant Quinti, 89; Barcelona (08041), Spain.
Rebeca Marin-BuenoDepartment of Neurology, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Carrer de Sant Quinti, 89; Barcelona (08041), Spain.
Alejandro HornickDepartment of Neurology, Southern Illinois Healthcare Memorial Hospital of Carbondale, 405 W Jackson Street, Carbondale (62901), Illinois, US.
Cristofol Vives-BauzaDepartment of Biology, Universitat de les Illes Balears, Carretera de Valldemossa, km 7,5, Palma (07122), Spain.
Rosa Diaz NavarroDepartment of Neurology, Hospital Universitari Son Espases, Universitat de les Illes Balears, Carretera de Valldemossa, 79, Palma (07120), Spain.
Silvia TurDepartment of Neurology, Hospital Universitari Son Espases, Universitat de les Illes Balears, Carretera de Valldemossa, 79, Palma (07120), Spain.
Carmen JimenezDepartment of Neurology, Hospital Universitari Son Espases, Universitat de les Illes Balears, Carretera de Valldemossa, 79, Palma (07120), Spain.
Victor ObachDepartment of Neurology, Hospital Clinic de Barcelona, Universitat de Barcelona, Carrer Villarroel, 170, Barcelona (08036), Spain.
Tomas SeguraResearch Unit, Complejo Hospitalario Universitario de Albacete. Calle Laurel s/n. Albacete (02008), Spain.
Gemma Serrano-HerasResearch Unit, Complejo Hospitalario Universitario de Albacete. Calle Laurel s/n. Albacete (02008), Spain.
Jong-Won ChungDepartment of Neurology, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul, South Korea.
Jaume RoquerNeurovascular Research Group, Institut Hospital del Mar de Investigations Mediques, Passeig Maritim, 25-29, Barcelona (08003), Spain.
Carol Soriano-TarragaDepartment of Psychiatry, Washington University School of Medicine, 660 S. Euclid Avenue, Saint Louis (63110), Missouri, US.
Eva Giralt-SteinhauerNeurovascular Research Group, Institut Hospital del Mar de Investigations Mediques, Passeig Maritim, 25-29, Barcelona (08003), Spain.
Marina Mola-CaminalNeurovascular Research Group, Institut Hospital del Mar de Investigations Mediques, Passeig Maritim, 25-29, Barcelona (08003), Spain.
Joanna PeraDepartment of Neurology, Jagiellonian University, Golebia, 24, Krakow(31-007), Poland.
Katarzyna Lapicka-BodziochDepartment of Neurology, Jagiellonian University, Golebia, 24, Krakow(31-007), Poland.
Justyna DerbiszDepartment of Neurology, Jagiellonian University, Golebia, 24, Krakow(31-007), Poland.
Antoni DavalosDepartment of Neurology, Hospital Germans Trias i Pujol, Universitat Autonoma de Barcelona, Carretera de Canyet, s/n; Badalona (08916), Spain.
Elena Lopez-CancioDepartment of Neurology, Hospital Universitario Central de Asturias, Oviedo, Spain.
Lucia MuñozDepartment of Neurology, Hospital Germans Trias i Pujol, Universitat Autonoma de Barcelona, Carretera de Canyet, s/n; Badalona (08916), Spain.
Turgut TatlisumakDepartment of Neurology, Sahlgrenska University Hospital, University of Gothenburg, Bla straket, 5; Gothenburg (413 45), Sweden.
Carlos MolinaStroke Unit, Vall d'Hebron University Hospital, Universitat de Barcelona, Passeig de la Vall d'Hebron, 1198; Barcelona (08035), Spain.
Marc RiboStroke Unit, Vall d'Hebron University Hospital, Universitat de Barcelona, Passeig de la Vall d'Hebron, 1198; Barcelona (08035), Spain.
Alejandro BustamanteDepartment of Neurology, Hospital Germans Trias i Pujol, Universitat Autonoma de Barcelona, Carretera de Canyet, s/n; Badalona (08916), Spain.
Tomas SobrinoClinical Neurosciences Research Laboratory, Health Research Institute of Santiago de Compostela (IDIS), Avda. Travesa da Choupana s/n; Santiago de Compostela (15706), Spain.
Jose Castillo-SanchezClinical Neurosciences Research Laboratory, Health Research Institute of Santiago de Compostela (IDIS), Avda. Travesa da Choupana s/n; Santiago de Compostela (15706), Spain.
Francisco CamposClinical Neurosciences Research Laboratory, Health Research Institute of Santiago de Compostela (IDIS), Avda. Travesa da Choupana s/n; Santiago de Compostela (15706), Spain.
Emilio Rodriguez-CastroClinical Neurosciences Research Laboratory, Health Research Institute of Santiago de Compostela (IDIS), Avda. Travesa da Choupana s/n; Santiago de Compostela (15706), Spain.
Susana Arias-RivasClinical Neurosciences Research Laboratory, Health Research Institute of Santiago de Compostela (IDIS), Avda. Travesa da Choupana s/n; Santiago de Compostela (15706), Spain.
Manuel Rodríguez-YáñezClinical Neurosciences Research Laboratory, Health Research Institute of Santiago de Compostela (IDIS), Avda. Travesa da Choupana s/n; Santiago de Compostela (15706), Spain.
Christina HerbosaDepartment of Neurology, Washington University School of Medicine, 660 S. Euclid Avenue; Campus Box 8111; Saint Louis (63110), Missouri, US.
Andria L FordDepartment of Neurology, Washington University School of Medicine, 660 S. Euclid Avenue; Campus Box 8111; Saint Louis (63110), Missouri, US.
Antonio ArauzInstituto Nacional de Neurologia y Neurocirurgia de Mexico, Avenida Insurgentes Sur 3877, Ciudad de Mexico (14269), Mexico.
Iscia Lopes-CendesDepartment of Neurology, School of Medical Sciences, University of Campinas (UNICAMP), R. Tessalia Viera de Camargo, 126; Cidade Universitaria, Campinas (13083-887), Brazil.
Theodore LowenkopfDepartment of Neurology, Providence St. Vincent Medical Center, 9205 SW Barnes Rd, Portland (97225), Oregon, US.
Miguel A BarbozaNeurosciences Department, Hospital Rafael A. Calderon Guardia, Avenidas 7 y 9, calles 15 y 17, Aranjuez, San José, Costa Rica.
Hajar AminiDepartment of Neurology and MIND Institute, University of California at Davis, 2825 5 street, Sacramento (95817), California, US.
Boryana StamovaDepartment of Neurology and MIND Institute, University of California at Davis, 2825 5 street, Sacramento (95817), California, US.
Bradley P AnderDepartment of Neurology and MIND Institute, University of California at Davis, 2825 5 street, Sacramento (95817), California, US.
Frank R SharpDepartment of Neurology and MIND Institute, University of California at Davis, 2825 5 street, Sacramento (95817), California, US.
Gyeong Moon KimDepartment of Neurology, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul, South Korea.
Oh Young BangDepartment of Neurology, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul, South Korea.
Jordi Jimenez-CondeNeurovascular Research Group, Institut Hospital del Mar de Investigations Mediques, Passeig Maritim, 25-29, Barcelona (08003), Spain.
Agnieszka SlowikDepartment of Neurology, Jagiellonian University, Golebia, 24, Krakow(31-007), Poland.
Daniel StribianDepartment of Neurology, Helsinki University Hospital, Haartmaninkatu 4 Rakennus 1, Helsinki (00290), Finland.
Ellen A TsaiTranslational Biology, Biogen, Inc, 115 Brodway, Cambridge (02142), Massachusetts, US.
Linda C BurklyGenetics and Neurodevelomental Disease Research Unit, Biogen, Inc, 115 Brodway, Cambridge (02142), Massachusetts, US.
Joan MontanerStroke Unit, Vall d'Hebron University Hospital, Universitat de Barcelona, Passeig de la Vall d'Hebron, 1198; Barcelona (08035), Spain.
Israel Fernandez-CadenasStroke Unit, Vall d'Hebron University Hospital, Universitat de Barcelona, Passeig de la Vall d'Hebron, 1198; Barcelona (08035), Spain.
Jin-Moo LeeDepartment of Neurology, Washington University School of Medicine, 660 S. Euclid Avenue; Campus Box 8111; Saint Louis (63110), Missouri, US.
Carlos CruchagaDepartment of Psychiatry, Washington University School of Medicine, 660 S. Euclid Avenue, Saint Louis (63110), Missouri, US.
Washington University in St. Louis · USUniversitat Autònoma de Barcelona · ESUniversidade de Santiago de Compostela · ESHebron University · PSJagiellonian University · PLUniversity of California Davis Medical Center · USHospital Del Mar · ESHospital Universitario Son Espases · ESSamsung Medical Center · KRBiogen (United States) · USComplejo Hospitalario Universitario de Albacete · ESUniversidade Estadual de Campinas (UNICAMP) · BRBarnes-Jewish Hospital · USHelsinki University Hospital · FIHospital Clínic de Barcelona · ESHospital Terrassa · ESHospital Universitario Central de Asturias · ESHospital Universitario Virgen del Rocío · ESHospital Universitario Virgen Macarena · ESInstituto Nacional de Neurología y Neurocirugía · MX
Funding
Molecular Biology of Stroke in HumansR01NS075035 · NINDS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI SHARP, FRANK R · 2012 to 2016
$3.1MGenomics of Intracerebral Hemorrhage and its CausesR01NS106950 · NINDS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI ANDER, BRADLEY PEARCE, SHARP, FRANK R · 2019 to 2023
$3.0MWhole Genome RNA Sequencing (RNAseq) of Blood from Patients with Lacunar StrokeR01NS101718 · NINDS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI SHARP, FRANK R, STAMOVA, BORYANA · 2017 to 2021
$3.0MWhole Transcriptome Studies of Patients with Transient Ischemic Attacks (TIAs)R01NS097000 · NINDS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI SHARP, FRANK R, STAMOVA, BORYANA · 2016 to 2020
$2.8MGenetic Architecture of Acute Human Brain IschemiaR01NS085419 · NINDS · WASHINGTON UNIVERSITY · PI CRUCHAGA, CARLOS, LEE, JIN-MOO · 2014 to 2018
$2.8MA Novel Approach to Assessing Cryptogenic StrokeR01NS079153 · NINDS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI SHARP, FRANK R · 2012 to 2016
$2.8MMid-America Regional Coordinating Center (MARCC)U24NS107230 · NINDS · WASHINGTON UNIVERSITY · PI Andria Lee Ford, Peter David Panagos · 2018 to 2026
$2.8MGENETICS OF EARLY NEUROLOGICAL INSTABILITY AFTER ISCHEMIC STROKE (GENISIS)K23NS099487 · NINDS · WASHINGTON UNIVERSITY · PI HEITSCH, LAURA · 2017 to 2021
$996kNINDS NIH HHS K23 NS099487NINDS NIH HHS R01 NS075035NINDS NIH HHS R01 NS079153NINDS NIH HHS R01 NS085419NINDS NIH HHS R01 NS097000NINDS NIH HHS R01 NS101718NINDS NIH HHS R01 NS106950NINDS NIH HHS U24 NS107230
Abstract
During the first hours after stroke onset neurological deficits can be highly unstable: some patients rapidly improve, while others deteriorate. This early neurological instability has a major impact on long-term outcome. Here, we aimed to determine the genetic architecture of early neurological instability measured by the difference between NIH stroke scale (NIHSS) within six hours of stroke onset and NIHSS at 24h (ΔNIHSS). A total of 5,876 individuals from seven countries (Spain, Finland, Poland, United States, Costa Rica, Mexico and Korea) were studied using a multi-ancestry meta-analyses. We found that 8.7% of ΔNIHSS variance was explained by common genetic variations, and also that early neurological instability has a different genetic architecture than that of stroke risk. Seven loci (2p25.1, 2q31.2, 2q33.3, 4q34.3, 5q33.2, 6q26 and 7p21.1) were genome-wide significant and explained 2.1% of the variability suggesting that additional variants influence early change in neurological deficits. We used functional genomics and bioinformatic annotation to identify the genes driving the association from each loci. eQTL mapping and SMR indicate that RESEARCH INTO CONTEXT:
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