Burden of Risk Alleles for Hypertension Increases Risk of Intracerebral Hemorrhage

被引：41

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

共 31 条

[1] Validation of self reported diagnosis of hypertension in a cohort of university graduates in Spain -: art. no. 94 [J].

Alonso, A ;

Beunza, JJ ;

Delgado-Rodríguez, M ;

Martínez-González, MA .

BMC PUBLIC HEALTH, 2005, 5 (1)

[2] A haplotype map of the human genome [J].

Altshuler, D ;

Brooks, LD ;

Chakravarti, A ;

Collins, FS ;

Daly, MJ ;

Donnelly, P ;

Gibbs, RA ;

Belmont, JW ;

Boudreau, A ;

Leal, SM ;

Hardenbol, P ;

Pasternak, S ;

Wheeler, DA ;

Willis, TD ;

Yu, FL ;

Yang, HM ;

Zeng, CQ ;

Gao, Y ;

Hu, HR ;

Hu, WT ;

Li, CH ;

Lin, W ;

Liu, SQ ;

Pan, H ;

Tang, XL ;

Wang, J ;

Wang, W ;

Yu, J ;

Zhang, B ;

Zhang, QR ;

Zhao, HB ;

Zhao, H ;

Zhou, J ;

Gabriel, SB ;

Barry, R ;

Blumenstiel, B ;

Camargo, A ;

Defelice, M ;

Faggart, M ;

Goyette, M ;

Gupta, S ;

Moore, J ;

Nguyen, H ;

Onofrio, RC ;

Parkin, M ;

Roy, J ;

Stahl, E ;

Winchester, E ;

Ziaugra, L ;

Shen, Y .

NATURE, 2005, 437 (7063) :1299-1320

[3] A map of human genome variation from population-scale sequencing [J].

Altshuler, David ;

Durbin, Richard M. ;

Abecasis, Goncalo R. ;

Bentley, David R. ;

Chakravarti, Aravinda ;

Clark, Andrew G. ;

Collins, Francis S. ;

De la Vega, Francisco M. ;

Donnelly, Peter ;

Egholm, Michael ;

Flicek, Paul ;

Gabriel, Stacey B. ;

Gibbs, Richard A. ;

Knoppers, Bartha M. ;

Lander, Eric S. ;

Lehrach, Hans ;

Mardis, Elaine R. ;

McVean, Gil A. ;

Nickerson, DebbieA. ;

Peltonen, Leena ;

Schafer, Alan J. ;

Sherry, Stephen T. ;

Wang, Jun ;

Wilson, Richard K. ;

Gibbs, Richard A. ;

Deiros, David ;

Metzker, Mike ;

Muzny, Donna ;

Reid, Jeff ;

Wheeler, David ;

Wang, Jun ;

Li, Jingxiang ;

Jian, Min ;

Li, Guoqing ;

Li, Ruiqiang ;

Liang, Huiqing ;

Tian, Geng ;

Wang, Bo ;

Wang, Jian ;

Wang, Wei ;

Yang, Huanming ;

Zhang, Xiuqing ;

Zheng, Huisong ;

Lander, Eric S. ;

Altshuler, David L. ;

Ambrogio, Lauren ;

Bloom, Toby ;

Cibulskis, Kristian ;

Fennell, Tim J. ;

Gabriel, Stacey B. .

NATURE, 2010, 467 (7319) :1061-1073

[4] Common Mitochondrial Sequence Variants in Ischemic Stroke [J].

Anderson, Christopher D. ;

Biffi, Alessandro ;

Rahman, Rosanna ;

Ross, Owen A. ;

Jagiella, Jeremiasz M. ;

Kissela, Brett ;

Cole, John W. ;

Cortellini, Lynelle ;

Rost, Natalia S. ;

Cheng, Yu-Ching ;

Greenberg, Steven M. ;

de Bakker, Paul I. W. ;

Brown, Robert D., Jr. ;

Brott, Thomas G. ;

Mitchell, Braxton D. ;

Broderick, Joseph P. ;

Worrall, Bradford B. ;

Furie, Karen L. ;

Kittner, Steven J. ;

Woo, Daniel ;

Slowik, Agnieszka ;

Meschia, James F. ;

Saxena, Richa ;

Rosand, Jonathan .

ANNALS OF NEUROLOGY, 2011, 69 (03) :471-480

[5] The Effect of Survival Bias on Case-Control Genetic Association Studies of Highly Lethal Diseases [J].

Anderson, Christopher D. ;

Nalls, Michael A. ;

Biffi, Alessandro ;

Rost, Natalia S. ;

Greenberg, Steven M. ;

Singleton, Andrew B. ;

Meschia, James F. ;

Rosand, Jonathan .

CIRCULATION-CARDIOVASCULAR GENETICS, 2011, 4 (02) :188-U265

[6] Variants at APOE Influence Risk of Deep and Lobar Intracerebral Hemorrhage [J].

Biffi, Alessandro ;

Sonni, Akshata ;

Anderson, Christopher D. ;

Kissela, Brett ;

Jagiella, Jeremiasz M. ;

Schmidt, Helena ;

Jimenez-Conde, Jordi ;

Hansen, Bjorn M. ;

Fernandez-Cadenas, Israel ;

Cortellini, Lynelle ;

Ayres, Alison ;

Schwab, Kristin ;

Juchniewicz, Karol ;

Urbanik, Andrzej ;

Rost, Natalia S. ;

Viswanathan, Anand ;

Seifert-Held, Thomas ;

Stoegerer, Eva-Maria ;

Tomas, Marta ;

Rabionet, Raquel ;

Estivill, Xavier ;

Brown, Devin L. ;

Silliman, Scott L. ;

Selim, Magdy ;

Worrall, Bradford B. ;

Meschia, James F. ;

Montaner, Joan ;

Lindgren, Arne ;

Roquer, Jaume ;

Schmidt, Reinhold ;

Greenberg, Steven M. ;

Slowik, Agnieszka ;

Broderick, Joseph P. ;

Woo, Daniel ;

Rosand, Jonathan .

ANNALS OF NEUROLOGY, 2010, 68 (06) :934-943

[7] HYPERTENSION AS A RISK FACTOR FOR SPONTANEOUS INTRACEREBRAL HEMORRHAGE [J].

BROTT, T ;

THALINGER, K ;

HERTZBERG, V .

STROKE, 1986, 17 (06) :1078-1083

[8]

Burns Joseph D., 2008, Comprehensive Therapy, V34, P183

[9] Exploiting Common Genetic Variation to Make Anticoagulation Safer [J].

Chang, Yuchiao ;

Cortellini, Lynelle ;

Greenberg, Steven M. ;

Rosand, Jonathan ;

Singer, Daniel ;

Schwab, Kristen ;

Selim, Magdy ;

Meschia, James ;

Eckman, Mark H. ;

Silliman, Scott ;

Brown, Devon ;

Worrall, W. Bradford ;

Tirschwell, David ;

Gage, Brian F. .

STROKE, 2009, 40 (03) :S64-S66

[10] VALIDATION OF QUESTIONNAIRE INFORMATION ON RISK-FACTORS AND DISEASE OUTCOMES IN A PROSPECTIVE COHORT STUDY OF WOMEN [J].

COLDITZ, GA ;

MARTIN, P ;

STAMPFER, MJ ;

WILLETT, WC ;

SAMPSON, L ;

ROSNER, B ;

HENNEKENS, CH ;

SPEIZER, FE .

AMERICAN JOURNAL OF EPIDEMIOLOGY, 1986, 123 (05) :894-900

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