Sangam: A Confluence of Knowledge Streams

Variants at APOE influence risk of deep and lobar intracerebral hemorrhage

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dc.contributor Stroke Program, Department of Neurology, University of Michigan Health System, Ann Harbor, MI
dc.contributor 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
dc.contributor 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
dc.contributor 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
dc.contributor Department of Neurology, University of Cincinnati College of Medicine, Cincinnati, OH
dc.contributor Department of Neurology, Jagiellonian University Medical College, Krakow, Poland
dc.contributor Institute of Molecular Biology and Medical Biochemistry, Medical University Graz, Austria
dc.contributor 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
dc.contributor Department of Clinical Sciences Lund Neurology, Lund University, Lund, Sweden ; Department of Neurology, SkÅne University Hospital, Lund, Sweden
dc.contributor Neurovascular Research Laboratory and Neurovascular Unit, Institut de Recerca, Hospital Vall d'Hebron, Universitat AutÒnoma de Barcelona, Barcelona, Spain
dc.contributor 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
dc.contributor Department of Neurology, Massachusetts General Hospital, Boston MA
dc.contributor Department of Neurology, Massachusetts General Hospital, Boston MA
dc.contributor Department of Neurology, Jagiellonian University Medical College, Krakow, Poland
dc.contributor Department of Neurology, Jagiellonian University Medical College, Krakow, Poland
dc.contributor 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
dc.contributor Department of Neurology, Massachusetts General Hospital, Boston MA
dc.contributor Department of Neurology, Medical University Graz, Austria
dc.contributor Department of Neurology, Medical University Graz, Austria
dc.contributor Genes and Disease Program, Center for Genomic Regulation (CRG), National Genotyping Center (CeGen), CIBERESP and Pompeu Fabra University (UPF), Barcelona, Spain
dc.contributor Genes and Disease Program, Center for Genomic Regulation (CRG), National Genotyping Center (CeGen), CIBERESP and Pompeu Fabra University (UPF), Barcelona, Spain
dc.contributor Genes and Disease Program, Center for Genomic Regulation (CRG), National Genotyping Center (CeGen), CIBERESP and Pompeu Fabra University (UPF), Barcelona, Spain
dc.contributor Department of Neurology, University of Florida College of Medicine, Jacksonville, FL
dc.contributor Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA
dc.contributor Department of Neurology and Public Health Sciences, University of Virginia Health System, Charlottesville, VA
dc.contributor Department of Neurology, Mayo Clinic, Jacksonville, FL
dc.contributor Neurovascular Research Laboratory and Neurovascular Unit, Institut de Recerca, Hospital Vall d'Hebron, Universitat AutÒnoma de Barcelona, Barcelona, Spain
dc.contributor Department of Clinical Sciences Lund Neurology, Lund University, Lund, Sweden ; Department of Neurology, SkÅne University Hospital, Lund, Sweden
dc.contributor 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
dc.contributor Department of Neurology, Medical University Graz, Austria
dc.contributor Department of Neurology, Massachusetts General Hospital, Boston MA
dc.contributor Department of Neurology, Jagiellonian University Medical College, Krakow, Poland
dc.contributor Department of Neurology, University of Cincinnati College of Medicine, Cincinnati, OH
dc.contributor Department of Neurology, University of Cincinnati College of Medicine, Cincinnati, OH
dc.contributor 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
dc.creator Biffi, Alessandro
dc.creator Sonni, Akshata
dc.creator Anderson, Christopher D.
dc.creator Kissela, Brett
dc.creator Jagiella, Jeremiasz M.
dc.creator Schmidt, Helena
dc.creator Jimenez-Conde, Jordi
dc.creator Hansen, Björn M.
dc.creator Fernandez-Cadenas, Israel
dc.creator Cortellini, Lynelle
dc.creator Ayres, Alison
dc.creator Schwab, Kristin
dc.creator Juchniewicz, Karol
dc.creator Urbanik, Andrzej
dc.creator Rost, Natalia S.
dc.creator Viswanathan, Anand
dc.creator Seifert-Held, Thomas
dc.creator Stoegerer, Eva-Maria
dc.creator Tomás, Marta
dc.creator Rabionet, Raquel
dc.creator Estivill, Xavier
dc.creator Brown, Devin L.
dc.creator Silliman, Scott L.
dc.creator Selim, Magdy
dc.creator Worrall, Bradford B.
dc.creator Meschia, James F.
dc.creator Montaner, Joan
dc.creator Lindgren, Arne
dc.creator Roquer, Jaume
dc.creator Schmidt, Reinhold
dc.creator Greenberg, Steven M.
dc.creator Slowik, Agnieszka
dc.creator Broderick, Joseph P.
dc.creator Woo, Daniel
dc.creator Rosand, Jonathan
dc.date 2011-01-04T16:22:20Z
dc.date 2011-03-01T16:26:42Z
dc.date 2010-12
dc.date.accessioned 2022-05-19T11:03:16Z
dc.date.available 2022-05-19T11:03:16Z
dc.identifier 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>
dc.identifier 0364-5134
dc.identifier 1531-8249
dc.identifier https://hdl.handle.net/2027.42/78478
dc.identifier 21061402
dc.identifier 10.1002/ana.22134
dc.identifier Annals of Neurology
dc.identifier.uri http://localhost:8080/xmlui/handle/CUHPOERS/102702
dc.description 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
dc.description Peer Reviewed
dc.description http://deepblue.lib.umich.edu/bitstream/2027.42/78478/1/22134_ftp.pdf
dc.format 263619 bytes
dc.format 3118 bytes
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dc.publisher Wiley Subscription Services, Inc., A Wiley Company
dc.rights IndexNoFollow
dc.subject Life and Medical Sciences
dc.subject Neuroscience, Neurology, and Psychiatry
dc.subject Psychiatry
dc.subject Health Sciences
dc.title Variants at APOE influence risk of deep and lobar intracerebral hemorrhage
dc.type Article


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