title: Genetic predisposition to higher blood pressure increases coronary artery disease risk.
abstract: Hypertension is a risk factor for coronary artery disease. Recent genome-wide association studies have identified 30 genetic variants associated with higher blood pressure at genome-wide significance (P<5 × 10(-8)). If elevated blood pressure is a causative factor for coronary artery disease, these variants should also increase coronary artery disease risk. Analyzing genome-wide association data from 22 233 coronary artery disease cases and 64 762 controls, we observed in the Coronary ARtery DIsease Genome-Wide Replication And Meta-Analysis (CARDIoGRAM) consortium that 88% of these blood pressure-associated polymorphisms were likewise positively associated with coronary artery disease, that is, they had an odds ratio >1 for coronary artery disease, a proportion much higher than expected by chance (P=4 × 10(-5)). The average relative coronary artery disease risk increase per each of the multiple blood pressure-raising alleles observed in the consortium was 3.0% for systolic blood pressure-associated polymorphisms (95% confidence interval, 1.8%-4.3%) and 2.9% for diastolic blood pressure-associated polymorphisms (95% confidence interval, 1.7%-4.1%). In substudies, individuals carrying most systolic blood pressure- and diastolic blood pressure-related risk alleles (top quintile of a genetic risk score distribution) had 70% (95% confidence interval, 50%-94%) and 59% (95% confidence interval, 40%-81%) higher odds of having coronary artery disease, respectively, as compared with individuals in the bottom quintile. In conclusion, most blood pressure-associated polymorphisms also confer an increased risk for coronary artery disease. These findings are consistent with a causal relationship of increasing blood pressure to coronary artery disease. Genetic variants primarily affecting blood pressure contribute to the genetic basis of coronary artery disease.
authors.affiliation: University Clinic Schleswig Holstein, Institute of Epidemiology, Campus Kiel, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Lieb
authors.forename: Henning
authors.initials: H
authors.lastname: Jansen
authors.forename: Christina
authors.initials: C
authors.lastname: Loley
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pencina
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Nelson
authors.forename: Christopher
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authors.lastname: Newton-Cheh
authors.forename: Sekar
authors.initials: S
authors.lastname: Kathiresan
authors.forename: Muredach P
authors.initials: MP
authors.lastname: Reilly
authors.forename: Themistocles L
authors.initials: TL
authors.lastname: Assimes
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: Alistair S
authors.initials: AS
authors.lastname: Hall
authors.forename: Christian
authors.initials: C
authors.lastname: Hengstenberg
authors.forename: Reijo
authors.initials: R
authors.lastname: Laaksonen
authors.forename: Ruth
authors.initials: R
authors.lastname: McPherson
authors.forename: Unnur
authors.initials: U
authors.lastname: Thorsteinsdottir
authors.forename: Andreas
authors.initials: A
authors.lastname: Ziegler
authors.forename: Annette
authors.initials: A
authors.lastname: Peters
authors.forename: John R
authors.initials: JR
authors.lastname: Thompson
authors.forename: Inke R
authors.initials: IR
authors.lastname: König
authors.forename: Jeanette
authors.initials: J
authors.lastname: Erdmann
authors.forename: Nilesh J
authors.initials: NJ
authors.lastname: Samani
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.forename: Heribert
authors.initials: H
authors.lastname: Schunkert
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001794:Blood Pressure / Q000235:genetics*; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000453:epidemiology* / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors