Genetic variants in CETP increase risk of intracerebral hemorrhage

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Genetic variants in CETP increase risk of intracerebral hemorrhage. / Anderson, Christopher D.; Falcone, Guido J.; Phuah, Chia-Ling; Radmanesh, Farid; Brouwers, H Bart; Battey, Thomas W K; Biffi, Alessandro; Peloso, Gina M.; Liu, Dajiang J; Ayres, Alison M.; Goldstein, Joshua N.; Viswanathan, Anand; Greenberg, Steven M.; Selim, Magdy; Meschia, James F.; Brown, Devin L.; Worrall, Bradford; Silliman, Scott L.; Tirschwell, David L.; Flaherty, Matthew L.; Kraft, Peter; Jagiella, Jeremiasz M.; Schmidt, Helena; Hansen, Björn M; Jimenez-Conde, Jordi; Giralt-Steinhauer, Eva; Elosua, Roberto; Cuadrado-Godia, Elisa; Soriano, Carolina; van Nieuwenhuizen, Koen M; Klijn, Catharina J. M.; Rannikmae, Kristiina; Samarasekera, Neshika; Al-Shahi Salman, Rustam; Sudlow, Catherine L; Deary, Ian J; Morotti, Andrea; Pezzini, Alessandro; Pera, Joanna; Urbanik, Andrzej; Pichler, Alexander; Enzinger, Christian; Norrving, Bo; Montaner, Joan; Fernandez-Cadenas, Israel; Delgado, Pilar; Roquer, Jaume; Lindgren, Arne; Slowik, Agnieszka; Schmidt, Reinhold; Global Lipids Genetics Consortium and International Stroke Genetics Consortium.

I: Annals of Neurology, Vol. 80, Nr. 5, 2016, s. 730-740.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Anderson, CD, Falcone, GJ, Phuah, C-L, Radmanesh, F, Brouwers, HB, Battey, TWK, Biffi, A, Peloso, GM, Liu, DJ, Ayres, AM, Goldstein, JN, Viswanathan, A, Greenberg, SM, Selim, M, Meschia, JF, Brown, DL, Worrall, B, Silliman, SL, Tirschwell, DL, Flaherty, ML, Kraft, P, Jagiella, JM, Schmidt, H, Hansen, BM, Jimenez-Conde, J, Giralt-Steinhauer, E, Elosua, R, Cuadrado-Godia, E, Soriano, C, van Nieuwenhuizen, KM, Klijn, CJM, Rannikmae, K, Samarasekera, N, Al-Shahi Salman, R, Sudlow, CL, Deary, IJ, Morotti, A, Pezzini, A, Pera, J, Urbanik, A, Pichler, A, Enzinger, C, Norrving, B, Montaner, J, Fernandez-Cadenas, I, Delgado, P, Roquer, J, Lindgren, A, Slowik, A, Schmidt, R & Global Lipids Genetics Consortium and International Stroke Genetics Consortium 2016, 'Genetic variants in CETP increase risk of intracerebral hemorrhage', Annals of Neurology, vol. 80, nr. 5, s. 730-740. https://doi.org/10.1002/ana.24780

APA

Anderson, C. D., Falcone, G. J., Phuah, C-L., Radmanesh, F., Brouwers, H. B., Battey, T. W. K., ... Global Lipids Genetics Consortium and International Stroke Genetics Consortium (2016). Genetic variants in CETP increase risk of intracerebral hemorrhage. Annals of Neurology, 80(5), 730-740. https://doi.org/10.1002/ana.24780

CBE

Anderson CD, Falcone GJ, Phuah C-L, Radmanesh F, Brouwers HB, Battey TWK, Biffi A, Peloso GM, Liu DJ, Ayres AM, Goldstein JN, Viswanathan A, Greenberg SM, Selim M, Meschia JF, Brown DL, Worrall B, Silliman SL, Tirschwell DL, Flaherty ML, Kraft P, Jagiella JM, Schmidt H, Hansen BM, Jimenez-Conde J, Giralt-Steinhauer E, Elosua R, Cuadrado-Godia E, Soriano C, van Nieuwenhuizen KM, Klijn CJM, Rannikmae K, Samarasekera N, Al-Shahi Salman R, Sudlow CL, Deary IJ, Morotti A, Pezzini A, Pera J, Urbanik A, Pichler A, Enzinger C, Norrving B, Montaner J, Fernandez-Cadenas I, Delgado P, Roquer J, Lindgren A, Slowik A, Schmidt R, Global Lipids Genetics Consortium and International Stroke Genetics Consortium. 2016. Genetic variants in CETP increase risk of intracerebral hemorrhage. Annals of Neurology. 80(5):730-740. https://doi.org/10.1002/ana.24780

MLA

Vancouver

Anderson CD, Falcone GJ, Phuah C-L, Radmanesh F, Brouwers HB, Battey TWK et al. Genetic variants in CETP increase risk of intracerebral hemorrhage. Annals of Neurology. 2016;80(5):730-740. https://doi.org/10.1002/ana.24780

Author

Anderson, Christopher D. ; Falcone, Guido J. ; Phuah, Chia-Ling ; Radmanesh, Farid ; Brouwers, H Bart ; Battey, Thomas W K ; Biffi, Alessandro ; Peloso, Gina M. ; Liu, Dajiang J ; Ayres, Alison M. ; Goldstein, Joshua N. ; Viswanathan, Anand ; Greenberg, Steven M. ; Selim, Magdy ; Meschia, James F. ; Brown, Devin L. ; Worrall, Bradford ; Silliman, Scott L. ; Tirschwell, David L. ; Flaherty, Matthew L. ; Kraft, Peter ; Jagiella, Jeremiasz M. ; Schmidt, Helena ; Hansen, Björn M ; Jimenez-Conde, Jordi ; Giralt-Steinhauer, Eva ; Elosua, Roberto ; Cuadrado-Godia, Elisa ; Soriano, Carolina ; van Nieuwenhuizen, Koen M ; Klijn, Catharina J. M. ; Rannikmae, Kristiina ; Samarasekera, Neshika ; Al-Shahi Salman, Rustam ; Sudlow, Catherine L ; Deary, Ian J ; Morotti, Andrea ; Pezzini, Alessandro ; Pera, Joanna ; Urbanik, Andrzej ; Pichler, Alexander ; Enzinger, Christian ; Norrving, Bo ; Montaner, Joan ; Fernandez-Cadenas, Israel ; Delgado, Pilar ; Roquer, Jaume ; Lindgren, Arne ; Slowik, Agnieszka ; Schmidt, Reinhold ; Global Lipids Genetics Consortium and International Stroke Genetics Consortium. / Genetic variants in CETP increase risk of intracerebral hemorrhage. I: Annals of Neurology. 2016 ; Vol. 80, Nr. 5. s. 730-740.

RIS

TY - JOUR

T1 - Genetic variants in CETP increase risk of intracerebral hemorrhage

AU - Anderson, Christopher D.

AU - Falcone, Guido J.

AU - Phuah, Chia-Ling

AU - Radmanesh, Farid

AU - Brouwers, H Bart

AU - Battey, Thomas W K

AU - Biffi, Alessandro

AU - Peloso, Gina M.

AU - Liu, Dajiang J

AU - Ayres, Alison M.

AU - Goldstein, Joshua N.

AU - Viswanathan, Anand

AU - Greenberg, Steven M.

AU - Selim, Magdy

AU - Meschia, James F.

AU - Brown, Devin L.

AU - Worrall, Bradford

AU - Silliman, Scott L.

AU - Tirschwell, David L.

AU - Flaherty, Matthew L.

AU - Kraft, Peter

AU - Jagiella, Jeremiasz M.

AU - Schmidt, Helena

AU - Hansen, Björn M

AU - Jimenez-Conde, Jordi

AU - Giralt-Steinhauer, Eva

AU - Elosua, Roberto

AU - Cuadrado-Godia, Elisa

AU - Soriano, Carolina

AU - van Nieuwenhuizen, Koen M

AU - Klijn, Catharina J. M.

AU - Rannikmae, Kristiina

AU - Samarasekera, Neshika

AU - Al-Shahi Salman, Rustam

AU - Sudlow, Catherine L

AU - Deary, Ian J

AU - Morotti, Andrea

AU - Pezzini, Alessandro

AU - Pera, Joanna

AU - Urbanik, Andrzej

AU - Pichler, Alexander

AU - Enzinger, Christian

AU - Norrving, Bo

AU - Montaner, Joan

AU - Fernandez-Cadenas, Israel

AU - Delgado, Pilar

AU - Roquer, Jaume

AU - Lindgren, Arne

AU - Slowik, Agnieszka

AU - Schmidt, Reinhold

AU - Global Lipids Genetics Consortium and International Stroke Genetics Consortium

N1 - © 2016 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Cerebral Hemorrhage

KW - Cholesterol Ester Transfer Proteins

KW - Cholesterol, HDL

KW - Female

KW - Genetic Predisposition to Disease

KW - Genotype

KW - Humans

KW - Male

KW - Middle Aged

KW - Polymorphism, Single Nucleotide

KW - Journal Article

KW - Research Support, N.I.H., Extramural

U2 - 10.1002/ana.24780

DO - 10.1002/ana.24780

M3 - Article

VL - 80

SP - 730

EP - 740

JO - Annals of Neurology

T2 - Annals of Neurology

JF - Annals of Neurology

SN - 1531-8249

IS - 5

ER -