Burden of risk alleles for hypertension increases risk of intracerebral hemorrhage

Guido J. Falcone, Alessandro Biffi, William J. Devan, Jeremiasz M. Jagiella, Helena Schmidt, Brett Kissela, Björn M. Hansen, Jordi Jimenez-Conde, Eva Giralt-Steinhauer, Roberto Elosua, Elisa Cuadrado-Godia, Carolina Soriano, Alison M. Ayres, Kristin Schwab, Joanna Pera, Andrzej Urbanik, Natalia S. Rost, Joshua N. Goldstein, Anand Viswanathan, Alexander Pichler & 23 others Christian Enzinger, Bo Norrving, David L. Tirschwell, Magdy Selim, Devin L. Brown, Scott L. Silliman, Bradford B. Worrall, James F. Meschia, Stella Kidwell, Joan Montaner, Israel Fernandez-Cadenas, Pilar Delgado, Joseph P. Broderick, Steven M. Greenberg, Jaume Roquer, Arne Lindgren, Agnieszka Slowik, Reinhold Schmidt, Matthew L. Flaherty, Dawn O. Kleindorfer, Carl D. Langefeld, Daniel Woo, Jonathan Rosand

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Background and Purpose-Genetic variation influences risk of intracerebral hemorrhage (ICH). Hypertension (HTN) is a potent risk factor for ICH and several common genetic variants (single nucleotide polymorphisms [SNPs]) associated with blood pressure levels have been identified. We sought to determine whether the cumulative burden of blood pressure-related SNPs is associated with risk of ICH and pre-ICH diagnosis of HTN. Methods-We conducted a prospective multicenter case-control study in 2272 subjects of European ancestry (1025 cases and 1247 control subjects). Thirty-nine SNPs reported to be associated with blood pressure levels were identified from the National Human Genome Research Institute genomewide association study catalog. Single-SNP association analyses were performed for the outcomes ICH and pre-ICH HTN. Subsequently, weighted and unweighted genetic risk scores were constructed using these SNPs and entered as the independent variable in logistic regression models with ICH and pre-ICH HTN as the dependent variables. Results-No single SNP was associated with either ICH or pre-ICH HTN. The blood pressure-based unweighted genetic risk score was associated with risk of ICH (OR, 1.11; 95% CI, 1.02-1.21; P=0.01) and the subset of ICH in deep regions (OR, 1.18; 95% CI, 1.07-1.30; P=0.001), but not with the subset of lobar ICH. The score was associated with a history of HTN among control subjects (OR, 1.17; 95% CI, 1.04-1.31; P=0.009) and ICH cases (OR, 1.15; 95% CI, 1.01-1.31; P=0.04). Similar results were obtained when using a weighted score. Conclusion-Increasing numbers of high blood pressure-related alleles are associated with increased risk of deep ICH as well as with clinically identified HTN.

Original languageEnglish (US)
Pages (from-to)2877-2883
Number of pages7
JournalStroke
Volume43
Issue number11
DOIs
StatePublished - Nov 2012
Externally publishedYes

Fingerprint

Cerebral Hemorrhage
Alleles
Hypertension
Single Nucleotide Polymorphism
Blood Pressure
National Human Genome Research Institute (U.S.)
Logistic Models
Case-Control Studies

Keywords

  • genetic risk score
  • genetics
  • hypertension
  • intracerebral hemorrhage

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Advanced and Specialized Nursing

Cite this

Falcone, G. J., Biffi, A., Devan, W. J., Jagiella, J. M., Schmidt, H., Kissela, B., ... Rosand, J. (2012). Burden of risk alleles for hypertension increases risk of intracerebral hemorrhage. Stroke, 43(11), 2877-2883. https://doi.org/10.1161/STROKEAHA.112.659755

Burden of risk alleles for hypertension increases risk of intracerebral hemorrhage. / Falcone, Guido J.; Biffi, Alessandro; Devan, William J.; Jagiella, Jeremiasz M.; Schmidt, Helena; Kissela, Brett; Hansen, Björn M.; Jimenez-Conde, Jordi; Giralt-Steinhauer, Eva; Elosua, Roberto; Cuadrado-Godia, Elisa; Soriano, Carolina; Ayres, Alison M.; Schwab, Kristin; Pera, Joanna; Urbanik, Andrzej; Rost, Natalia S.; Goldstein, Joshua N.; Viswanathan, Anand; Pichler, Alexander; Enzinger, Christian; Norrving, Bo; Tirschwell, David L.; Selim, Magdy; Brown, Devin L.; Silliman, Scott L.; Worrall, Bradford B.; Meschia, James F.; Kidwell, Stella; Montaner, Joan; Fernandez-Cadenas, Israel; Delgado, Pilar; Broderick, Joseph P.; Greenberg, Steven M.; Roquer, Jaume; Lindgren, Arne; Slowik, Agnieszka; Schmidt, Reinhold; Flaherty, Matthew L.; Kleindorfer, Dawn O.; Langefeld, Carl D.; Woo, Daniel; Rosand, Jonathan.

In: Stroke, Vol. 43, No. 11, 11.2012, p. 2877-2883.

Research output: Contribution to journalArticle

Falcone, GJ, Biffi, A, Devan, WJ, Jagiella, JM, Schmidt, H, Kissela, B, Hansen, BM, Jimenez-Conde, J, Giralt-Steinhauer, E, Elosua, R, Cuadrado-Godia, E, Soriano, C, Ayres, AM, Schwab, K, Pera, J, Urbanik, A, Rost, NS, Goldstein, JN, Viswanathan, A, Pichler, A, Enzinger, C, Norrving, B, Tirschwell, DL, Selim, M, Brown, DL, Silliman, SL, Worrall, BB, Meschia, JF, Kidwell, S, Montaner, J, Fernandez-Cadenas, I, Delgado, P, Broderick, JP, Greenberg, SM, Roquer, J, Lindgren, A, Slowik, A, Schmidt, R, Flaherty, ML, Kleindorfer, DO, Langefeld, CD, Woo, D & Rosand, J 2012, 'Burden of risk alleles for hypertension increases risk of intracerebral hemorrhage', Stroke, vol. 43, no. 11, pp. 2877-2883. https://doi.org/10.1161/STROKEAHA.112.659755
Falcone GJ, Biffi A, Devan WJ, Jagiella JM, Schmidt H, Kissela B et al. Burden of risk alleles for hypertension increases risk of intracerebral hemorrhage. Stroke. 2012 Nov;43(11):2877-2883. https://doi.org/10.1161/STROKEAHA.112.659755
Falcone, Guido J. ; Biffi, Alessandro ; Devan, William J. ; Jagiella, Jeremiasz M. ; Schmidt, Helena ; Kissela, Brett ; Hansen, Björn M. ; Jimenez-Conde, Jordi ; Giralt-Steinhauer, Eva ; Elosua, Roberto ; Cuadrado-Godia, Elisa ; Soriano, Carolina ; Ayres, Alison M. ; Schwab, Kristin ; Pera, Joanna ; Urbanik, Andrzej ; Rost, Natalia S. ; Goldstein, Joshua N. ; Viswanathan, Anand ; Pichler, Alexander ; Enzinger, Christian ; Norrving, Bo ; Tirschwell, David L. ; Selim, Magdy ; Brown, Devin L. ; Silliman, Scott L. ; Worrall, Bradford B. ; Meschia, James F. ; Kidwell, Stella ; Montaner, Joan ; Fernandez-Cadenas, Israel ; Delgado, Pilar ; Broderick, Joseph P. ; Greenberg, Steven M. ; Roquer, Jaume ; Lindgren, Arne ; Slowik, Agnieszka ; Schmidt, Reinhold ; Flaherty, Matthew L. ; Kleindorfer, Dawn O. ; Langefeld, Carl D. ; Woo, Daniel ; Rosand, Jonathan. / Burden of risk alleles for hypertension increases risk of intracerebral hemorrhage. In: Stroke. 2012 ; Vol. 43, No. 11. pp. 2877-2883.
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title = "Burden of risk alleles for hypertension increases risk of intracerebral hemorrhage",
abstract = "Background and Purpose-Genetic variation influences risk of intracerebral hemorrhage (ICH). Hypertension (HTN) is a potent risk factor for ICH and several common genetic variants (single nucleotide polymorphisms [SNPs]) associated with blood pressure levels have been identified. We sought to determine whether the cumulative burden of blood pressure-related SNPs is associated with risk of ICH and pre-ICH diagnosis of HTN. Methods-We conducted a prospective multicenter case-control study in 2272 subjects of European ancestry (1025 cases and 1247 control subjects). Thirty-nine SNPs reported to be associated with blood pressure levels were identified from the National Human Genome Research Institute genomewide association study catalog. Single-SNP association analyses were performed for the outcomes ICH and pre-ICH HTN. Subsequently, weighted and unweighted genetic risk scores were constructed using these SNPs and entered as the independent variable in logistic regression models with ICH and pre-ICH HTN as the dependent variables. Results-No single SNP was associated with either ICH or pre-ICH HTN. The blood pressure-based unweighted genetic risk score was associated with risk of ICH (OR, 1.11; 95{\%} CI, 1.02-1.21; P=0.01) and the subset of ICH in deep regions (OR, 1.18; 95{\%} CI, 1.07-1.30; P=0.001), but not with the subset of lobar ICH. The score was associated with a history of HTN among control subjects (OR, 1.17; 95{\%} CI, 1.04-1.31; P=0.009) and ICH cases (OR, 1.15; 95{\%} CI, 1.01-1.31; P=0.04). Similar results were obtained when using a weighted score. Conclusion-Increasing numbers of high blood pressure-related alleles are associated with increased risk of deep ICH as well as with clinically identified HTN.",
keywords = "genetic risk score, genetics, hypertension, intracerebral hemorrhage",
author = "Falcone, {Guido J.} and Alessandro Biffi and Devan, {William J.} and Jagiella, {Jeremiasz M.} and Helena Schmidt and Brett Kissela and Hansen, {Bj{\"o}rn M.} and Jordi Jimenez-Conde and Eva Giralt-Steinhauer and Roberto Elosua and Elisa Cuadrado-Godia and Carolina Soriano and Ayres, {Alison M.} and Kristin Schwab and Joanna Pera and Andrzej Urbanik and Rost, {Natalia S.} and Goldstein, {Joshua N.} and Anand Viswanathan and Alexander Pichler and Christian Enzinger and Bo Norrving and Tirschwell, {David L.} and Magdy Selim and Brown, {Devin L.} and Silliman, {Scott L.} and Worrall, {Bradford B.} and Meschia, {James F.} and Stella Kidwell and Joan Montaner and Israel Fernandez-Cadenas and Pilar Delgado and Broderick, {Joseph P.} and Greenberg, {Steven M.} and Jaume Roquer and Arne Lindgren and Agnieszka Slowik and Reinhold Schmidt and Flaherty, {Matthew L.} and Kleindorfer, {Dawn O.} and Langefeld, {Carl D.} and Daniel Woo and Jonathan Rosand",
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TY - JOUR

T1 - Burden of risk alleles for hypertension increases risk of intracerebral hemorrhage

AU - Falcone, Guido J.

AU - Biffi, Alessandro

AU - Devan, William J.

AU - Jagiella, Jeremiasz M.

AU - Schmidt, Helena

AU - Kissela, Brett

AU - Hansen, Björn M.

AU - Jimenez-Conde, Jordi

AU - Giralt-Steinhauer, Eva

AU - Elosua, Roberto

AU - Cuadrado-Godia, Elisa

AU - Soriano, Carolina

AU - Ayres, Alison M.

AU - Schwab, Kristin

AU - Pera, Joanna

AU - Urbanik, Andrzej

AU - Rost, Natalia S.

AU - Goldstein, Joshua N.

AU - Viswanathan, Anand

AU - Pichler, Alexander

AU - Enzinger, Christian

AU - Norrving, Bo

AU - Tirschwell, David L.

AU - Selim, Magdy

AU - Brown, Devin L.

AU - Silliman, Scott L.

AU - Worrall, Bradford B.

AU - Meschia, James F.

AU - Kidwell, Stella

AU - Montaner, Joan

AU - Fernandez-Cadenas, Israel

AU - Delgado, Pilar

AU - Broderick, Joseph P.

AU - Greenberg, Steven M.

AU - Roquer, Jaume

AU - Lindgren, Arne

AU - Slowik, Agnieszka

AU - Schmidt, Reinhold

AU - Flaherty, Matthew L.

AU - Kleindorfer, Dawn O.

AU - Langefeld, Carl D.

AU - Woo, Daniel

AU - Rosand, Jonathan

PY - 2012/11

Y1 - 2012/11

N2 - Background and Purpose-Genetic variation influences risk of intracerebral hemorrhage (ICH). Hypertension (HTN) is a potent risk factor for ICH and several common genetic variants (single nucleotide polymorphisms [SNPs]) associated with blood pressure levels have been identified. We sought to determine whether the cumulative burden of blood pressure-related SNPs is associated with risk of ICH and pre-ICH diagnosis of HTN. Methods-We conducted a prospective multicenter case-control study in 2272 subjects of European ancestry (1025 cases and 1247 control subjects). Thirty-nine SNPs reported to be associated with blood pressure levels were identified from the National Human Genome Research Institute genomewide association study catalog. Single-SNP association analyses were performed for the outcomes ICH and pre-ICH HTN. Subsequently, weighted and unweighted genetic risk scores were constructed using these SNPs and entered as the independent variable in logistic regression models with ICH and pre-ICH HTN as the dependent variables. Results-No single SNP was associated with either ICH or pre-ICH HTN. The blood pressure-based unweighted genetic risk score was associated with risk of ICH (OR, 1.11; 95% CI, 1.02-1.21; P=0.01) and the subset of ICH in deep regions (OR, 1.18; 95% CI, 1.07-1.30; P=0.001), but not with the subset of lobar ICH. The score was associated with a history of HTN among control subjects (OR, 1.17; 95% CI, 1.04-1.31; P=0.009) and ICH cases (OR, 1.15; 95% CI, 1.01-1.31; P=0.04). Similar results were obtained when using a weighted score. Conclusion-Increasing numbers of high blood pressure-related alleles are associated with increased risk of deep ICH as well as with clinically identified HTN.

AB - Background and Purpose-Genetic variation influences risk of intracerebral hemorrhage (ICH). Hypertension (HTN) is a potent risk factor for ICH and several common genetic variants (single nucleotide polymorphisms [SNPs]) associated with blood pressure levels have been identified. We sought to determine whether the cumulative burden of blood pressure-related SNPs is associated with risk of ICH and pre-ICH diagnosis of HTN. Methods-We conducted a prospective multicenter case-control study in 2272 subjects of European ancestry (1025 cases and 1247 control subjects). Thirty-nine SNPs reported to be associated with blood pressure levels were identified from the National Human Genome Research Institute genomewide association study catalog. Single-SNP association analyses were performed for the outcomes ICH and pre-ICH HTN. Subsequently, weighted and unweighted genetic risk scores were constructed using these SNPs and entered as the independent variable in logistic regression models with ICH and pre-ICH HTN as the dependent variables. Results-No single SNP was associated with either ICH or pre-ICH HTN. The blood pressure-based unweighted genetic risk score was associated with risk of ICH (OR, 1.11; 95% CI, 1.02-1.21; P=0.01) and the subset of ICH in deep regions (OR, 1.18; 95% CI, 1.07-1.30; P=0.001), but not with the subset of lobar ICH. The score was associated with a history of HTN among control subjects (OR, 1.17; 95% CI, 1.04-1.31; P=0.009) and ICH cases (OR, 1.15; 95% CI, 1.01-1.31; P=0.04). Similar results were obtained when using a weighted score. Conclusion-Increasing numbers of high blood pressure-related alleles are associated with increased risk of deep ICH as well as with clinically identified HTN.

KW - genetic risk score

KW - genetics

KW - hypertension

KW - intracerebral hemorrhage

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