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 PichlerChristian Enzinger, Bo Norrving, David L. Tirschwell, Magdy Selim, Devin L. Brown, Scott L. Silliman, Bradford B. Worrall, James F. Meschia, Chelsea S. 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 journalArticlepeer-review

23 Scopus citations


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
Issue number11
StatePublished - Nov 2012


  • genetic risk score
  • genetics
  • hypertension
  • intracerebral hemorrhage

ASJC Scopus subject areas

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


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