Burden of Risk Alleles for Hypertension Increases Risk of Intracerebral Hemorrhage

被引：40

作者：

Falcone, Guido J. ^{[1
,2
,3
,5
,6
]}

Biffi, Alessandro ^{[1
,2
,3
,5
]}

Devan, William J. ^{[1
,2
,3
,5
]}

Jagiella, Jeremiasz M. ^{[7
]}

Schmidt, Helena ^{[9
]}

Kissela, Brett ^{[10
]}

Hansen, Bjoern M. ^{[11
,12
]}

Jimenez-Conde, Jordi ^{[13
,14
]}

Giralt-Steinhauer, Eva ^{[13
,14
]}

Elosua, Roberto ^{[14
]}

Cuadrado-Godia, Elisa ^{[13
,14
]}

Soriano, Carolina ^{[13
,14
]}

Ayres, Alison M. ^{[1
]}

Schwab, Kristin ^{[1
]}

Pera, Joanna ^{[7
]}

Urbanik, Andrzej ^{[8
]}

Rost, Natalia S. ^{[1
,2
,3
,5
]}

Goldstein, Joshua N. ^{[4
]}

Viswanathan, Anand ^{[2
]}

Pichler, Alexander ^{[15
]}

Enzinger, Christian ^{[15
,16
]}

Norrving, Bo ^{[11
,12
]}

Tirschwell, David L. ^{[17
]}

Selim, Magdy ^{[18
]}

Brown, Devin L. ^{[19
]}

Silliman, Scott L. ^{[20
]}

Worrall, Bradford B. ^{[21
]}

Meschia, James F. ^{[22
]}

Kidwell, Chelsea S. ^{[23
]}

Montaner, Joan ^{[24
,25
]}

Fernandez-Cadenas, Israel ^{[24
,25
]}

Delgado, Pilar ^{[24
,25
]}

Broderick, Joseph P. ^{[10
]}

Greenberg, Steven M. ^{[2
]}

Roquer, Jaume ^{[13
]}

Lindgren, Arne ^{[11
,12
]}

Slowik, Agnieszka ^{[7
]}

Schmidt, Reinhold ^{[15
]}

Flaherty, Matthew L. ^{[10
]}

Kleindorfer, Dawn O. ^{[10
]}

Langefeld, Carl D. ^{[26
]}

Woo, Daniel ^{[10
]}

Rosand, Jonathan ^{[1
]}

机构：

[1] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

[2] Massachusetts Gen Hosp, Hemorrhag Stroke Res Grp, Boston, MA 02114 USA

[3] Massachusetts Gen Hosp, Dept Neurol, Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA

[4] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA

[5] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA

[6] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[7] Jagiellonian Univ, Coll Med, Dept Neurol, Krakow, Poland

[8] Jagiellonian Univ, Coll Med, Dept Radiol, Krakow, Poland

[9] Med Univ Graz, Inst Mol Biol & Med Biochem, Graz, Austria

[10] Univ Cincinnati, Coll Med, Dept Neurol, Cincinnati, OH USA

[11] Lund Univ, Dept Clin Sci Lund, Lund, Sweden

[12] Skane Univ Hosp, Dept Neurol, Lund, Sweden

[13] Univ Autonoma Barcelona, Hosp del Mar, Dept Neurol, Neurovasc Res Unit, E-08193 Barcelona, Spain

[14] Univ Autonoma Barcelona, Hosp del Mar, Program Inflammat & Cardiovasc Disorders, Inst Municipal Invest Med, E-08193 Barcelona, Spain

[15] Med Univ Graz, Dept Neurol, Graz, Austria

[16] Med Univ Graz, Dept Radiol, Neuroradiol Sect, Graz, Austria

[17] Univ Washington, Harborview Med Ctr, Stroke Ctr, Seattle, WA 98104 USA

[18] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA

[19] Univ Michigan Hlth Syst, Dept Neurol, Stroke Program, Ann Arbor, MI USA

[20] Univ Florida, Coll Med, Dept Neurol, Jacksonville, FL USA

[21] Univ Virginia Hlth Syst, Dept Neurol & Publ Hlth Sci, Charlottesville, VA USA

[22] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA

[23] Georgetown Univ, Med Ctr, Dept Neurol, Washington, DC 20007 USA

[24] Univ Autonoma Barcelona, Hosp Vall dHebron, Inst Recerca, Neurovasc Res Lab, E-08193 Barcelona, Spain

[25] Univ Autonoma Barcelona, Hosp Vall dHebron, Inst Recerca, Neurovasc Unit, E-08193 Barcelona, Spain

[26] Wake Forest Univ, Dept Biostat Sci, Winston Salem, NC 27109 USA

来源：

STROKE | 2012年 / 43卷 / 11期

基金：

奥地利科学基金会; 美国国家卫生研究院; 瑞典研究理事会;

关键词：

genetic risk score; genetics; hypertension; intracerebral hemorrhage; GENOME-WIDE ASSOCIATION; BLOOD-PRESSURE; PATHOPHYSIOLOGY; VALIDATION; VARIANTS; GENOTYPE; SEQUENCE; COHORT; STROKE;

D O I：

10.1161/STROKEAHA.112.659755

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.)

引用

页码：2877 / U183

页数：15

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