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, Chelsea S.
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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U2 - 10.1161/STROKEAHA.112.659755
DO - 10.1161/STROKEAHA.112.659755
M3 - Article
C2 - 22933587
AN - SCOPUS:84868206096
SN - 0039-2499
VL - 43
SP - 2877
EP - 2883
JO - Stroke
JF - Stroke
IS - 11
ER -