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Lieb, W.* ; Jansen, H.* ; Loley, C.* ; Pencina, M.J.* ; Nelson, C.P.* ; Newton-Cheh, C.* ; Kathiresan, S.* ; Reilly, M.P.* ; Assimes, T.L.* ; Boerwinkle, E.* ; Hall, A.S.* ; Hengstenberg, C.* ; Laaksonen, R.* ; McPherson, R.* ; Thorsteinsdottir, U.* ; Ziegler, A.* ; Peters, A. ; Thompson, J.R.* ; König, I.R.* ; Erdmann, J.* ; Samani, N.J.* ; Vasan, R.S.* ; Schunkert, H.*

Genetic predisposition to higher blood pressure increases coronary artery disease risk.

Hypertension 61, 995-1001 (2013)

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Open Access Green as soon as Postprint is submitted to ZB.

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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<5x10(-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=4x10(-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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Blood Pressure ; Coronary Artery Disease ; Genetics ; Polymorphism; Genome-wide Association ; Regression Dilution ; Heart-disease ; Follow-up ; Hypertension ; Metaanalysis ; Loci ; Phenotypes ; Design ; Trials

ISSN (print) / ISBN 0194-911x

e-ISSN 1524-4563

Journal Hypertension

Quellenangaben Volume: 61, Issue: 5, Pages: 995-1001

Publisher Lippincott Williams & Wilkins

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Epidemiology II (EPI2)