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  • Pfeiffer, DorotheaUniversity Hospital Heidelberg (author)

Genetic Imbalance Is Associated With Functional Outcome After Ischemic Stroke

  • Article/chapterEnglish2019

Publisher, publication year, extent ...

  • 2019
  • 7 s.

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  • LIBRIS-ID:oai:lup.lub.lu.se:6883f323-7ec1-4fed-855c-6bad162c346f
  • https://lup.lub.lu.se/record/6883f323-7ec1-4fed-855c-6bad162c346fURI
  • https://doi.org/10.1161/STROKEAHA.118.021856DOI

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  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • 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.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Chen, BowangSouthern University of Science and Technology (author)
  • Schlicht, KristinaUniversity Medical Center Schleswig-Holstein,University of Kiel (author)
  • Ginsbach, PhilipUniversity of Edinburgh (author)
  • Abboud, SherineUniversité Libre de Bruxelles (ULB) (author)
  • Bersano, AnnaCarlo Besta Neurological Institute, IRCCS (author)
  • Bevan, SteveUniversity of Lincoln (author)
  • Brandt, TobiasSuva/Swiss National Accident Insurance Fund,University Hospital Heidelberg (author)
  • Caso, ValeriaOspedale Santa Maria della Misericordia (author)
  • Debette, StéphanieUniversity of Bordeaux,Centre Hospitalier Universitaire de Bordeaux (author)
  • Erhart, PhilippUniversity Hospital Heidelberg (author)
  • Freitag-Wolf, SandraUniversity Medical Center Schleswig-Holstein,University of Kiel (author)
  • Giacalone, GiacomoSan Raffaele Hospital (author)
  • Grau, Armin J.Klinikum Ludwigshafen (author)
  • Hayani, EyadUniversity Hospital Heidelberg (author)
  • Jern, ChristinaUniversity of Gothenburg,Sahlgrenska University Hospital (author)
  • Jiménez-Conde, JordiAutonomous University of Barcelona (author)
  • Kloss, ManjaUniversity Hospital Heidelberg (author)
  • Krawczak, MichaelUniversity Medical Center Schleswig-Holstein,University of Kiel (author)
  • Lee, Jin MooWashington University in St. Louis (author)
  • Lemmens, RobinUniversity Hospitals Leuven,Catholic University of Leuven (author)
  • Leys, DidierUniversity of Lille (author)
  • Lichy, ChristophMunicipal Hospital Memmingen (author)
  • Maguire, Jane M.University of Technology Sydney,University of Newcastle (author)
  • Martin, Juan J.Sanatorio Allende De Córdoba (author)
  • Metso, Antti J.Helsinki University Central Hospital (author)
  • Metso, Tiina M.Helsinki University Central Hospital (author)
  • Mitchell, Braxton D.University of Maryland,Baltimore Veterans Administration Medical Center (author)
  • Pezzini, AlessandroUniversity of Brescia (author)
  • Rosand, JonathanMassachusetts General Hospital (author)
  • Rost, Natalia S.Massachusetts General Hospital (author)
  • Stenman, MartinLund University,Lunds universitet,Klinisk strokeforskning,Forskargrupper vid Lunds universitet,Clinical Stroke Research Group,Lund University Research Groups,Skåne University Hospital(Swepub:lu)ma4276st (author)
  • Tatlisumak, TurgutUniversity of Gothenburg,Sahlgrenska University Hospital,Helsinki University Central Hospital (author)
  • Thijs, VincentUniversity of Melbourne,Austin Health (author)
  • Touzé, EmmanuelCentre Hospitalier Sainte-Anne,University of Caen Normandy (author)
  • Traenka, ChristopherUniversity Hospital Basel (author)
  • Werner, IngeUniversity Hospital Heidelberg (author)
  • Woo, DanielUniversity of Cincinnati (author)
  • Del Zotto, ElisabettaUniversity of Brescia (author)
  • Engelter, Stefan T.University Hospital Basel,Felix Platter Hospital,University of Basel (author)
  • Kittner, Steven J.University of Maryland,Baltimore Veterans Administration Medical Center (author)
  • Cole, John W.University of Maryland,Baltimore Veterans Administration Medical Center (author)
  • Grond-Ginsbach, CasparUniversity Hospital Heidelberg (author)
  • Lyrer, Philippe A.University Hospital Basel (author)
  • Lindgren, ArneLund University,Lunds universitet,Klinisk strokeforskning,Forskargrupper vid Lunds universitet,Clinical Stroke Research Group,Lund University Research Groups(Swepub:lu)neur-ali (author)
  • University Hospital HeidelbergSouthern University of Science and Technology (creator_code:org_t)

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  • In:Stroke50:2, s. 298-3041524-4628

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