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  • Marini, SandroMassachusetts General Hospital (author)

17p12 Influences Hematoma Volume and Outcome in Spontaneous Intracerebral Hemorrhage

  • Article/chapterEnglish2018

Publisher, publication year, extent ...

  • 2018
  • 8 s.

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:09e4fb26-3135-4d8f-ae83-c8c40e1b0c21
  • https://lup.lub.lu.se/record/09e4fb26-3135-4d8f-ae83-c8c40e1b0c21URI
  • https://doi.org/10.1161/STROKEAHA.117.020091DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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

Notes

  • Background and Purpose-Hematoma volume is an important determinant of clinical outcome in spontaneous intracerebral hemorrhage (ICH). We performed a genome-wide association study (GWAS) of hematoma volume with the aim of identifying novel biological pathways involved in the pathophysiology of primary brain injury in ICH. Methods-We conducted a 2-stage (discovery and replication) case-only genome-wide association study in patients with ICH of European ancestry. We utilized the admission head computed tomography to calculate hematoma volume via semiautomated computer-Assisted technique. After quality control and imputation, 7 million genetic variants were available for association testing with ICH volume, which was performed separately in lobar and nonlobar ICH cases using linear regression. Signals with P<5×10- 8 were pursued in replication and tested for association with admission Glasgow coma scale and 3-month post-ICH dichotomized (0-2 versus 3-6) modified Rankin Scale using ordinal and logistic regression, respectively. Results-The discovery phase included 394 ICH cases (228 lobar and 166 nonlobar) and identified 2 susceptibility loci: A genomic region on 22q13 encompassing PARVB (top single-nucleotide polymorphism rs9614326: β, 1.84; SE, 0.32; P=4.4×10-8) for lobar ICH volume and an intergenic region overlying numerous copy number variants on 17p12 (top single-nucleotide polymorphism rs11655160: β, 0.95; SE, 0.17; P=4.3×10-8) for nonlobar ICH volume. The replication included 240 ICH cases (71 lobar and 169 nonlobar) and corroborated the association for 17p12 (P=0.04; meta-Analysis P=2.5×10-9; heterogeneity, P=0.16) but not for 22q13 (P=0.49). In multivariable analysis, rs11655160 was also associated with lower admission Glasgow coma scale (odds ratio, 0.17; P=0.004) and increased risk of poor 3-month modified Rankin Scale (odds ratio, 1.94; P=0.045). Conclusions-We identified 17p12 as a novel susceptibility risk locus for hematoma volume, clinical severity, and functional outcome in nonlobar ICH. Replication in other ethnicities and follow-up translational studies are needed to elucidate the mechanism mediating the observed association.

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

  • Devan, William J.Massachusetts General Hospital (author)
  • Radmanesh, FaridMassachusetts General Hospital (author)
  • Miyares, LauraYale University,Massachusetts General Hospital (author)
  • Poterba, TimothyHarvard University (author)
  • Hansen, Björn M.Lund University,Lunds universitet,Klinisk strokeforskning,Forskargrupper vid Lunds universitet,Clinical Stroke Research Group,Lund University Research Groups,Skåne University Hospital(Swepub:lu)med-bhe (author)
  • Norrving, BoLund University,Lunds universitet,Klinisk strokeforskning,Forskargrupper vid Lunds universitet,Clinical Stroke Research Group,Lund University Research Groups,Skåne University Hospital(Swepub:lu)neur-bno (author)
  • Jimenez-Conde, JordiHospital del Mar Medical Research Institute (author)
  • Giralt-Steinhauer, EvaHospital del Mar Medical Research Institute (author)
  • Elosua, RobertoHospital del Mar Medical Research Institute (author)
  • Cuadrado-Godia, ElisaHospital del Mar Medical Research Institute (author)
  • Soriano, CarolinaHospital del Mar Medical Research Institute (author)
  • Roquer, JaumeHospital del Mar Medical Research Institute (author)
  • Kourkoulis, Christina E.Massachusetts General Hospital (author)
  • Ayres, Alison M.Autonomous University of Barcelona,Massachusetts General Hospital (author)
  • Schwab, KristinAutonomous University of Barcelona,Massachusetts General Hospital (author)
  • Tirschwell, David L.University of Washington (author)
  • Selim, MagdyBeth Israel Deaconess Medical Center (author)
  • Brown, Devin L.University of Michigan (author)
  • Silliman, Scott L.University of Florida (author)
  • Worrall, Bradford B.University of Virginia Health System (author)
  • Meschia, James F.Mayo Clinic Florida (author)
  • Kidwell, Chelsea S.University of Arizona (author)
  • Montaner, JoanVall d'Hebron University Hospital (author)
  • Fernandez-Cadenas, IsraelVall d'Hebron University Hospital,Hospital de Sant Pau (author)
  • Delgado, PilarVall d'Hebron University Hospital (author)
  • Greenberg, Steven M.Massachusetts General Hospital,Autonomous University of Barcelona (author)
  • Lindgren, ArneLund University,Lunds universitet,Klinisk strokeforskning,Forskargrupper vid Lunds universitet,Clinical Stroke Research Group,Lund University Research Groups,Skåne University Hospital(Swepub:lu)neur-ali (author)
  • Matouk, CharlesMassachusetts General Hospital,Yale University (author)
  • Sheth, Kevin N.Yale University,Massachusetts General Hospital (author)
  • Woo, DanielUniversity of Cincinnati (author)
  • Anderson, Christopher D.Massachusetts General Hospital,Broad Institute (author)
  • Rosand, JonathanBroad Institute,Massachusetts General Hospital (author)
  • Falcone, Guido J.Yale University,Massachusetts General Hospital (author)
  • Massachusetts General HospitalYale University (creator_code:org_t)

Related titles

  • In:Stroke49:7, s. 1618-16250039-2499

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