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FältnamnIndikatorerMetadata
00005520naa a2200925 4500
001oai:gup.ub.gu.se/281732
003SwePub
008240910s2019 | |||||||||||000 ||eng|
024a https://gup.ub.gu.se/publication/2817322 URI
024a https://doi.org/10.1161/strokeaha.118.0218562 DOI
040 a (SwePub)gu
041 a eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
100a Pfeiffer, D.4 aut
2451 0a Genetic Imbalance Is Associated With Functional Outcome After Ischemic Stroke
264 1b Ovid Technologies (Wolters Kluwer Health),c 2019
520 a 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.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Neurovetenskaper0 (SwePub)301052 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Neurosciences0 (SwePub)301052 hsv//eng
653 a DNA copy number variations
653 a genetics
653 a polymorphism
653 a single nucleotide
653 a prognosis
653 a stroke
653 a copy-number variation
653 a genome-wide
653 a ohnologs
653 a risk
700a Chen, B.4 aut
700a Schlicht, K.4 aut
700a Ginsbach, P.4 aut
700a Abboud, S.4 aut
700a Bersano, A.4 aut
700a Bevan, S.4 aut
700a Brandt, T.4 aut
700a Caso, V.4 aut
700a Debette, S.4 aut
700a Erhart, P.4 aut
700a Freitag-Wolf, S.4 aut
700a Giacalone, G.4 aut
700a Grau, A. J.4 aut
700a Hayani, E.4 aut
700a Jern, Christina,d 1962u Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology4 aut0 (Swepub:gu)xjerch
700a Jimenez-Conde, J.4 aut
700a Kloss, M.4 aut
700a Krawczak, M.4 aut
700a Lee, J. M.4 aut
700a Lemmens, R.4 aut
700a Leys, D.4 aut
700a Lichy, C.4 aut
700a Maguire, J. M.4 aut
700a Martin, J. J.4 aut
700a Metso, A. J.4 aut
700a Metso, T. M.4 aut
700a Mitchell, B. D.4 aut
700a Pezzini, A.4 aut
700a Rosand, J.4 aut
700a Rost, N. S.4 aut
700a Stenman, M.4 aut
700a Tatlisumak, Turgutu Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology4 aut0 (Swepub:gu)xtatlt
700a Thijs, V.4 aut
700a Touze, E.4 aut
700a Traenka, C.4 aut
700a Werner, I.4 aut
700a Woo, D.4 aut
700a Del Zotto, E.4 aut
700a Engelter, S. T.4 aut
700a Kittner, S. J.4 aut
700a Cole, J. W.4 aut
700a Grond-Ginsbach, C.4 aut
700a Lyrer, P. A.4 aut
700a Lindgren, A.4 aut
710a Göteborgs universitetb Institutionen för neurovetenskap och fysiologi4 org
773t Stroked : Ovid Technologies (Wolters Kluwer Health)g 50:2, s. 298-304q 50:2<298-304x 0039-2499x 1524-4628
856u https://www.ahajournals.org/doi/pdf/10.1161/STROKEAHA.118.021856
8564 8u https://gup.ub.gu.se/publication/281732
8564 8u https://doi.org/10.1161/strokeaha.118.021856

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