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Genetic variants in...
Genetic variants in CETP increase risk of intracerebral hemorrhage
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- Anderson, Christopher D. (author)
- Broad Institute
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- Falcone, Guido J. (author)
- Broad Institute
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- Phuah, Chia-Ling (author)
- Broad Institute
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- Radmanesh, Farid (author)
- Broad Institute
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- Brouwers, H Bart (author)
- Broad Institute
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- Battey, Thomas W K (author)
- Broad Institute
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- Biffi, Alessandro (author)
- Broad Institute
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- Peloso, Gina M. (author)
- Broad Institute
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- Liu, Dajiang J (author)
- Pennsylvania State University College of Medicine
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- Ayres, Alison M. (author)
- Massachusetts General Hospital
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Goldstein, Joshua N. (author)
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Viswanathan, Anand (author)
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Greenberg, Steven M. (author)
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Selim, Magdy (author)
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Meschia, James F. (author)
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Brown, Devin L. (author)
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Worrall, Bradford (author)
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Silliman, Scott L. (author)
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Tirschwell, David L. (author)
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Flaherty, Matthew L. (author)
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Kraft, Peter (author)
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Jagiella, Jeremiasz M. (author)
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Schmidt, Helena (author)
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- Hansen, Björn M (author)
- Lund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital
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Jimenez-Conde, Jordi (author)
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Giralt-Steinhauer, Eva (author)
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Elosua, Roberto (author)
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Cuadrado-Godia, Elisa (author)
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Soriano, Carolina (author)
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van Nieuwenhuizen, Koen M (author)
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Klijn, Catharina J. M. (author)
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Rannikmae, Kristiina (author)
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Samarasekera, Neshika (author)
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Al-Shahi Salman, Rustam (author)
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Sudlow, Catherine L (author)
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Deary, Ian J (author)
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Morotti, Andrea (author)
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Pezzini, Alessandro (author)
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Pera, Joanna (author)
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Urbanik, Andrzej (author)
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Pichler, Alexander (author)
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Enzinger, Christian (author)
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- Norrving, Bo (author)
- Lund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital
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Montaner, Joan (author)
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Fernandez-Cadenas, Israel (author)
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Delgado, Pilar (author)
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Roquer, Jaume (author)
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- Lindgren, Arne (author)
- Lund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital
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Slowik, Agnieszka (author)
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Schmidt, Reinhold (author)
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- 2016-10-19
- 2016
- English 11 s.
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In: Annals of Neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 80:5, s. 730-740
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Abstract
Subject headings
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- OBJECTIVE: In observational epidemiologic studies, higher plasma high-density lipoprotein cholesterol (HDL-C) has been associated with increased risk of intracerebral hemorrhage (ICH). DNA sequence variants that decrease cholesteryl ester transfer protein (CETP) gene activity increase plasma HDL-C; as such, medicines that inhibit CETP and raise HDL-C are in clinical development. Here, we test the hypothesis that CETP DNA sequence variants associated with higher HDL-C also increase risk for ICH.METHODS: We performed 2 candidate-gene analyses of CETP. First, we tested individual CETP variants in a discovery cohort of 1,149 ICH cases and 1,238 controls from 3 studies, followed by replication in 1,625 cases and 1,845 controls from 5 studies. Second, we constructed a genetic risk score comprised of 7 independent variants at the CETP locus and tested this score for association with HDL-C as well as ICH risk.RESULTS: Twelve variants within CETP demonstrated nominal association with ICH, with the strongest association at the rs173539 locus (odds ratio [OR] = 1.25, standard error [SE] = 0.06, p = 6.0 × 10(-4) ) with no heterogeneity across studies (I(2) = 0%). This association was replicated in patients of European ancestry (p = 0.03). A genetic score of CETP variants found to increase HDL-C by ∼2.85mg/dl in the Global Lipids Genetics Consortium was strongly associated with ICH risk (OR = 1.86, SE = 0.13, p = 1.39 × 10(-6) ).INTERPRETATION: Genetic variants in CETP associated with increased HDL-C raise the risk of ICH. Given ongoing therapeutic development in CETP inhibition and other HDL-raising strategies, further exploration of potential adverse cerebrovascular outcomes may be warranted. Ann Neurol 2016;80:730-740.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Keyword
- Adult
- Aged
- Cerebral Hemorrhage
- Cholesterol Ester Transfer Proteins
- Cholesterol, HDL
- Female
- Genetic Predisposition to Disease
- Genotype
- Humans
- Male
- Middle Aged
- Polymorphism, Single Nucleotide
- Journal Article
- Research Support, N.I.H., Extramural
Publication and Content Type
- art (subject category)
- ref (subject category)
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Anderson, Christ ...
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Falcone, Guido J ...
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Phuah, Chia-Ling
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Radmanesh, Farid
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Brouwers, H Bart
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Battey, Thomas W ...
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show more...
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Biffi, Alessandr ...
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Peloso, Gina M.
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Liu, Dajiang J
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Ayres, Alison M.
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Goldstein, Joshu ...
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Viswanathan, Ana ...
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Greenberg, Steve ...
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Selim, Magdy
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Meschia, James F ...
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Brown, Devin L.
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Worrall, Bradfor ...
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Silliman, Scott ...
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Tirschwell, Davi ...
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Flaherty, Matthe ...
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Kraft, Peter
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Jagiella, Jeremi ...
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Schmidt, Helena
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Hansen, Björn M
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Jimenez-Conde, J ...
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Giralt-Steinhaue ...
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Elosua, Roberto
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Cuadrado-Godia, ...
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Soriano, Carolin ...
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van Nieuwenhuize ...
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Klijn, Catharina ...
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Rannikmae, Krist ...
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Samarasekera, Ne ...
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Al-Shahi Salman, ...
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Sudlow, Catherin ...
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Deary, Ian J
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Morotti, Andrea
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Pezzini, Alessan ...
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Pera, Joanna
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Urbanik, Andrzej
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Pichler, Alexand ...
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Enzinger, Christ ...
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Norrving, Bo
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Montaner, Joan
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Fernandez-Cadena ...
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Delgado, Pilar
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Roquer, Jaume
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Lindgren, Arne
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Slowik, Agnieszk ...
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Schmidt, Reinhol ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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Annals of Neurol ...
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Lund University