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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 LU ; Jimenez-Conde, Jordi; Giralt-Steinhauer, Eva and Elosua, Roberto, et al. (2012) In Stroke: a journal of cerebral circulation 43(11). p.2877-2883
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.... (More)
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. (Stroke. 2012; 43: 2877-2883.) (Less)
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publication status
published
subject
keywords
genetic risk score, genetics, hypertension, intracerebral hemorrhage
in
Stroke: a journal of cerebral circulation
volume
43
issue
11
pages
2877 - 2883
publisher
American Heart Association
external identifiers
  • wos:000310432800270
  • scopus:84868206096
ISSN
1524-4628
DOI
10.1161/STROKEAHA.112.659755
language
English
LU publication?
yes
id
af705086-f48f-48b9-9d5a-8ef641ccb871 (old id 3388415)
date added to LUP
2013-02-01 07:04:12
date last changed
2017-06-11 04:15:30
@article{af705086-f48f-48b9-9d5a-8ef641ccb871,
  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. (Stroke. 2012; 43: 2877-2883.)},
  author       = {Falcone, Guido J. and Biffi, Alessandro and Devan, William J. and Jagiella, Jeremiasz M. and Schmidt, Helena and Kissela, Brett and Hansen, Björn and Jimenez-Conde, Jordi and Giralt-Steinhauer, Eva and Elosua, Roberto and Cuadrado-Godia, Elisa and Soriano, Carolina and Ayres, Alison M. and Schwab, Kristin and Pera, Joanna and Urbanik, Andrzej and Rost, Natalia S. and Goldstein, Joshua N. and Viswanathan, Anand and Pichler, Alexander and Enzinger, Christian and Norrving, Bo and Tirschwell, David L. and Selim, Magdy and Brown, Devin L. and Silliman, Scott L. and Worrall, Bradford B. and Meschia, James F. and Kidwell, Chelsea S. and Montaner, Joan and Fernandez-Cadenas, Israel and Delgado, Pilar and Broderick, Joseph P. and Greenberg, Steven M. and Roquer, Jaume and Lindgren, Arne and Slowik, Agnieszka and Schmidt, Reinhold and Flaherty, Matthew L. and Kleindorfer, Dawn O. and Langefeld, Carl D. and Woo, Daniel and Rosand, Jonathan},
  issn         = {1524-4628},
  keyword      = {genetic risk score,genetics,hypertension,intracerebral hemorrhage},
  language     = {eng},
  number       = {11},
  pages        = {2877--2883},
  publisher    = {American Heart Association},
  series       = { Stroke: a journal of cerebral circulation},
  title        = {Burden of Risk Alleles for Hypertension Increases Risk of Intracerebral Hemorrhage},
  url          = {http://dx.doi.org/10.1161/STROKEAHA.112.659755},
  volume       = {43},
  year         = {2012},
}