title: Burden of risk alleles for hypertension increases risk of intracerebral hemorrhage.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Increasing numbers of high blood pressure-related alleles are associated with increased risk of deep ICH as well as with clinically identified HTN.
authors.affiliation: Center for Human Genetic Research, Department of Neurology, Massachusetts General Hospital, and Department of Epidemiology, Harvard School of Public Health, 185 Cambridge Street; CPZN-6818, Boston, MA 02114, USA.
authors.forename: Guido J
authors.initials: GJ
authors.lastname: Falcone
authors.forename: Alessandro
authors.initials: A
authors.lastname: Biffi
authors.forename: William J
authors.initials: WJ
authors.lastname: Devan
authors.forename: Jeremiasz M
authors.initials: JM
authors.lastname: Jagiella
authors.forename: Helena
authors.initials: H
authors.lastname: Schmidt
authors.forename: Brett
authors.initials: B
authors.lastname: Kissela
authors.forename: Björn M
authors.initials: BM
authors.lastname: Hansen
authors.forename: Jordi
authors.initials: J
authors.lastname: Jimenez-Conde
authors.forename: Eva
authors.initials: E
authors.lastname: Giralt-Steinhauer
authors.forename: Roberto
authors.initials: R
authors.lastname: Elosua
authors.forename: Elisa
authors.initials: E
authors.lastname: Cuadrado-Godia
authors.forename: Carolina
authors.initials: C
authors.lastname: Soriano
authors.forename: Alison M
authors.initials: AM
authors.lastname: Ayres
authors.forename: Kristin
authors.initials: K
authors.lastname: Schwab
authors.forename: Joanna
authors.initials: J
authors.lastname: Pera
authors.forename: Andrzej
authors.initials: A
authors.lastname: Urbanik
authors.forename: Natalia S
authors.initials: NS
authors.lastname: Rost
authors.forename: Joshua N
authors.initials: JN
authors.lastname: Goldstein
authors.forename: Anand
authors.initials: A
authors.lastname: Viswanathan
authors.forename: Alexander
authors.initials: A
authors.lastname: Pichler
authors.forename: Christian
authors.initials: C
authors.lastname: Enzinger
authors.forename: Bo
authors.initials: B
authors.lastname: Norrving
authors.forename: David L
authors.initials: DL
authors.lastname: Tirschwell
authors.forename: Magdy
authors.initials: M
authors.lastname: Selim
authors.forename: Devin L
authors.initials: DL
authors.lastname: Brown
authors.forename: Scott L
authors.initials: SL
authors.lastname: Silliman
authors.forename: Bradford B
authors.initials: BB
authors.lastname: Worrall
authors.forename: James F
authors.initials: JF
authors.lastname: Meschia
authors.forename: Chelsea S
authors.initials: CS
authors.lastname: Kidwell
authors.forename: Joan
authors.initials: J
authors.lastname: Montaner
authors.forename: Israel
authors.initials: I
authors.lastname: Fernandez-Cadenas
authors.forename: Pilar
authors.initials: P
authors.lastname: Delgado
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Broderick
authors.forename: Steven M
authors.initials: SM
authors.lastname: Greenberg
authors.forename: Jaume
authors.initials: J
authors.lastname: Roquer
authors.forename: Arne
authors.initials: A
authors.lastname: Lindgren
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Slowik
authors.forename: Reinhold
authors.initials: R
authors.lastname: Schmidt
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Flaherty
authors.forename: Dawn O
authors.initials: DO
authors.lastname: Kleindorfer
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: Daniel
authors.initials: D
authors.lastname: Woo
authors.forename: Jonathan
authors.initials: J
authors.lastname: Rosand
mesh_terms: D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000235:genetics*; D020299:Intracranial Hemorrhage, Hypertensive / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors