Variants at APOE influence risk of deep and lobar intracerebral hemorrhage
dc.contributor.author | Biffi, Alessandro | en_US |
dc.contributor.author | Sonni, Akshata | en_US |
dc.contributor.author | Anderson, Christopher D. | en_US |
dc.contributor.author | Kissela, Brett | en_US |
dc.contributor.author | Jagiella, Jeremiasz M. | en_US |
dc.contributor.author | Schmidt, Helena | en_US |
dc.contributor.author | Jimenez-Conde, Jordi | en_US |
dc.contributor.author | Hansen, Björn M. | en_US |
dc.contributor.author | Fernandez-Cadenas, Israel | en_US |
dc.contributor.author | Cortellini, Lynelle | en_US |
dc.contributor.author | Ayres, Alison | en_US |
dc.contributor.author | Schwab, Kristin | en_US |
dc.contributor.author | Juchniewicz, Karol | en_US |
dc.contributor.author | Urbanik, Andrzej | en_US |
dc.contributor.author | Rost, Natalia S. | en_US |
dc.contributor.author | Viswanathan, Anand | en_US |
dc.contributor.author | Seifert-Held, Thomas | en_US |
dc.contributor.author | Stoegerer, Eva-Maria | en_US |
dc.contributor.author | Tomás, Marta | en_US |
dc.contributor.author | Rabionet, Raquel | en_US |
dc.contributor.author | Estivill, Xavier | en_US |
dc.contributor.author | Brown, Devin L. | en_US |
dc.contributor.author | Silliman, Scott L. | en_US |
dc.contributor.author | Selim, Magdy | en_US |
dc.contributor.author | Worrall, Bradford B. | en_US |
dc.contributor.author | Meschia, James F. | en_US |
dc.contributor.author | Montaner, Joan | en_US |
dc.contributor.author | Lindgren, Arne | en_US |
dc.contributor.author | Roquer, Jaume | en_US |
dc.contributor.author | Schmidt, Reinhold | en_US |
dc.contributor.author | Greenberg, Steven M. | en_US |
dc.contributor.author | Slowik, Agnieszka | en_US |
dc.contributor.author | Broderick, Joseph P. | en_US |
dc.contributor.author | Woo, Daniel | en_US |
dc.contributor.author | Rosand, Jonathan | en_US |
dc.date.accessioned | 2011-01-04T16:22:20Z | |
dc.date.available | 2011-03-01T16:26:42Z | en_US |
dc.date.issued | 2010-12 | en_US |
dc.identifier.citation | Biffi, Alessandro; Sonni, Akshata; Anderson, Christopher D.; Kissela, Brett; Jagiella, Jeremiasz M.; Schmidt, Helena; Jimenez-Conde, Jordi; Hansen, BjÖrn M.; Fernandez-Cadenas, Israel; Cortellini, Lynelle; Ayres, Alison; Schwab, Kristin; Juchniewicz, Karol; Urbanik, Andrzej; Rost, Natalia S.; Viswanathan, Anand; Seifert-Held, Thomas; Stoegerer, Eva-Maria; TomÁs, Marta; Rabionet, Raquel; Estivill, Xavier; Brown, Devin L.; Silliman, Scott L.; Selim, Magdy; Worrall, Bradford B.; Meschia, James F.; Montaner, Joan; Lindgren, Arne; Roquer, Jaume; Schmidt, Reinhold; Greenberg, Steven M.; Slowik, Agnieszka; Broderick, Joseph P.; Woo, Daniel; Rosand, Jonathan (2010). "Variants at APOE influence risk of deep and lobar intracerebral hemorrhage." Annals of Neurology 68(6): 934-943. <http://hdl.handle.net/2027.42/78478> | en_US |
dc.identifier.issn | 0364-5134 | en_US |
dc.identifier.issn | 1531-8249 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/78478 | |
dc.description.abstract | Objective Prior studies investigating the association between APOE alleles ε2/ε4 and risk of intracerebral hemorrhage (ICH) have been inconsistent and limited to small sample sizes, and did not account for confounding by population stratification or determine which genetic risk model was best applied. Methods We performed a large-scale genetic association study of 2189 ICH cases and 4041 controls from 7 cohorts, which were analyzed using additive models for ε2 and ε4. Results were subsequently meta-analyzed using a random effects model. A proportion of the individuals (322 cases, 357 controls) had available genome-wide data to adjust for population stratification. Results Alleles ε2 and ε4 were associated with lobar ICH at genome-wide significance levels (odds ratio [OR] = 1.82, 95% confidence interval [CI] = 1.50–2.23, p = 6.6 × 10 −10 ; and OR = 2.20, 95%CI = 1.85–2.63, p = 2.4 × 10 −11 , respectively). Restriction of analysis to definite/probable cerebral amyloid angiopathy ICH uncovered a stronger effect. Allele ε4 was also associated with increased risk for deep ICH (OR = 1.21, 95% CI = 1.08–1.36, p = 2.6 × 10 −4 ). Risk prediction evaluation identified the additive model as best for describing the effect of APOE genotypes. Interpretation APOE ε2 and ε4 are independent risk factors for lobar ICH, consistent with their known associations with amyloid biology. In addition, we present preliminary findings on a novel association between APOE ε4 and deep ICH. Finally, we demonstrate that an additive model for these APOE variants is superior to other forms of genetic risk modeling previously applied. ANN NEUROL 2010 | en_US |
dc.format.extent | 263619 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.subject.other | Neuroscience, Neurology, and Psychiatry | en_US |
dc.title | Variants at APOE influence risk of deep and lobar intracerebral hemorrhage | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Psychiatry | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Stroke Program, Department of Neurology, University of Michigan Health System, Ann Harbor, MI | en_US |
dc.contributor.affiliationother | Center for Human Genetic Research, Massachusetts General Hospital, Boston MA ; Department of Neurology, Massachusetts General Hospital, Boston MA ; Program in Medical and Population Genetics, Broad Institute, Cambridge MA | en_US |
dc.contributor.affiliationother | Center for Human Genetic Research, Massachusetts General Hospital, Boston MA ; Department of Neurology, Massachusetts General Hospital, Boston MA ; Program in Medical and Population Genetics, Broad Institute, Cambridge MA | en_US |
dc.contributor.affiliationother | Center for Human Genetic Research, Massachusetts General Hospital, Boston MA ; Department of Neurology, Massachusetts General Hospital, Boston MA ; Program in Medical and Population Genetics, Broad Institute, Cambridge MA | en_US |
dc.contributor.affiliationother | Department of Neurology, University of Cincinnati College of Medicine, Cincinnati, OH | en_US |
dc.contributor.affiliationother | Department of Neurology, Jagiellonian University Medical College, Krakow, Poland | en_US |
dc.contributor.affiliationother | Institute of Molecular Biology and Medical Biochemistry, Medical University Graz, Austria | en_US |
dc.contributor.affiliationother | Neurovascular Research Unit, Department of Neurology, Institut Municipal d'InvestigaciÓ Medica-Hospital del Mar, Universitat Autonoma de Barcelona, Barcelona, Spain ; Program in Inflammation and Cardiovascular Disorders, Institut Municipal d'InvestigaciÓ Medica-Hospital del Mar, Universitat Autonoma de Barcelona, Barcelona, Spain | en_US |
dc.contributor.affiliationother | Department of Clinical Sciences Lund Neurology, Lund University, Lund, Sweden ; Department of Neurology, SkÅne University Hospital, Lund, Sweden | en_US |
dc.contributor.affiliationother | Neurovascular Research Laboratory and Neurovascular Unit, Institut de Recerca, Hospital Vall d'Hebron, Universitat AutÒnoma de Barcelona, Barcelona, Spain | en_US |
dc.contributor.affiliationother | Center for Human Genetic Research, Massachusetts General Hospital, Boston MA ; Department of Neurology, Massachusetts General Hospital, Boston MA ; Program in Medical and Population Genetics, Broad Institute, Cambridge MA | en_US |
dc.contributor.affiliationother | Department of Neurology, Massachusetts General Hospital, Boston MA | en_US |
dc.contributor.affiliationother | Department of Neurology, Massachusetts General Hospital, Boston MA | en_US |
dc.contributor.affiliationother | Department of Neurology, Jagiellonian University Medical College, Krakow, Poland | en_US |
dc.contributor.affiliationother | Department of Neurology, Jagiellonian University Medical College, Krakow, Poland | en_US |
dc.contributor.affiliationother | Center for Human Genetic Research, Massachusetts General Hospital, Boston MA ; Department of Neurology, Massachusetts General Hospital, Boston MA ; Program in Medical and Population Genetics, Broad Institute, Cambridge MA | en_US |
dc.contributor.affiliationother | Department of Neurology, Massachusetts General Hospital, Boston MA | en_US |
dc.contributor.affiliationother | Department of Neurology, Medical University Graz, Austria | en_US |
dc.contributor.affiliationother | Department of Neurology, Medical University Graz, Austria | en_US |
dc.contributor.affiliationother | Genes and Disease Program, Center for Genomic Regulation (CRG), National Genotyping Center (CeGen), CIBERESP and Pompeu Fabra University (UPF), Barcelona, Spain | en_US |
dc.contributor.affiliationother | Genes and Disease Program, Center for Genomic Regulation (CRG), National Genotyping Center (CeGen), CIBERESP and Pompeu Fabra University (UPF), Barcelona, Spain | en_US |
dc.contributor.affiliationother | Genes and Disease Program, Center for Genomic Regulation (CRG), National Genotyping Center (CeGen), CIBERESP and Pompeu Fabra University (UPF), Barcelona, Spain | en_US |
dc.contributor.affiliationother | Department of Neurology, University of Florida College of Medicine, Jacksonville, FL | en_US |
dc.contributor.affiliationother | Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA | en_US |
dc.contributor.affiliationother | Department of Neurology and Public Health Sciences, University of Virginia Health System, Charlottesville, VA | en_US |
dc.contributor.affiliationother | Department of Neurology, Mayo Clinic, Jacksonville, FL | en_US |
dc.contributor.affiliationother | Neurovascular Research Laboratory and Neurovascular Unit, Institut de Recerca, Hospital Vall d'Hebron, Universitat AutÒnoma de Barcelona, Barcelona, Spain | en_US |
dc.contributor.affiliationother | Department of Clinical Sciences Lund Neurology, Lund University, Lund, Sweden ; Department of Neurology, SkÅne University Hospital, Lund, Sweden | en_US |
dc.contributor.affiliationother | Neurovascular Research Unit, Department of Neurology, Institut Municipal d'InvestigaciÓ Medica-Hospital del Mar, Universitat Autonoma de Barcelona, Barcelona, Spain ; Program in Inflammation and Cardiovascular Disorders, Institut Municipal d'InvestigaciÓ Medica-Hospital del Mar, Universitat Autonoma de Barcelona, Barcelona, Spain | en_US |
dc.contributor.affiliationother | Department of Neurology, Medical University Graz, Austria | en_US |
dc.contributor.affiliationother | Department of Neurology, Massachusetts General Hospital, Boston MA | en_US |
dc.contributor.affiliationother | Department of Neurology, Jagiellonian University Medical College, Krakow, Poland | en_US |
dc.contributor.affiliationother | Department of Neurology, University of Cincinnati College of Medicine, Cincinnati, OH | en_US |
dc.contributor.affiliationother | Department of Neurology, University of Cincinnati College of Medicine, Cincinnati, OH | en_US |
dc.contributor.affiliationother | Center for Human Genetic Research, Massachusetts General Hospital, Boston MA ; Department of Neurology, Massachusetts General Hospital, Boston MA ; Program in Medical and Population Genetics, Broad Institute, Cambridge MA ; Center for Human Genetic Research, Massachusetts General Hospital, 185 Cambridge Street, CPZN-6818, Boston, MA 02114 | en_US |
dc.identifier.pmid | 21061402 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/78478/1/22134_ftp.pdf | |
dc.identifier.doi | 10.1002/ana.22134 | en_US |
dc.identifier.source | Annals of Neurology | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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