Genetic predisposition to higher blood pressure increases coronary artery disease risk
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Genetic predisposition to higher blood pressure increases coronary artery disease risk. / Lieb, Wolfgang; Jansen, Henning; Loley, Christina; Pencina, Michael J; Nelson, Christopher P; Newton-Cheh, Christopher; Kathiresan, Sekar; Reilly, Muredach P; Assimes, Themistocles L; Boerwinkle, Eric; Hall, Alistair S; Hengstenberg, Christian; Laaksonen, Reijo; McPherson, Ruth; Thorsteinsdottir, Unnur; Ziegler, Andreas; Peters, Annette; Thompson, John R; König, Inke R; Erdmann, Jeanette; Samani, Nilesh J; Vasan, Ramachandran S; Schunkert, Heribert; CARDIoGRAM Consortium.
in: HYPERTENSION, Jahrgang 61, Nr. 5, 05.2013, S. 995-1001.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Genetic predisposition to higher blood pressure increases coronary artery disease risk
AU - Lieb, Wolfgang
AU - Jansen, Henning
AU - Loley, Christina
AU - Pencina, Michael J
AU - Nelson, Christopher P
AU - Newton-Cheh, Christopher
AU - Kathiresan, Sekar
AU - Reilly, Muredach P
AU - Assimes, Themistocles L
AU - Boerwinkle, Eric
AU - Hall, Alistair S
AU - Hengstenberg, Christian
AU - Laaksonen, Reijo
AU - McPherson, Ruth
AU - Thorsteinsdottir, Unnur
AU - Ziegler, Andreas
AU - Peters, Annette
AU - Thompson, John R
AU - König, Inke R
AU - Erdmann, Jeanette
AU - Samani, Nilesh J
AU - Vasan, Ramachandran S
AU - Schunkert, Heribert
AU - CARDIoGRAM Consortium
AU - Zeller, Tanja
AU - Blankenberg, Stefan
PY - 2013/5
Y1 - 2013/5
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Alleles
KW - Blood Pressure/genetics
KW - Case-Control Studies
KW - Coronary Artery Disease/epidemiology
KW - Female
KW - Genetic Predisposition to Disease/genetics
KW - Genome-Wide Association Study
KW - Humans
KW - Hypertension/genetics
KW - Male
KW - Middle Aged
KW - Polymorphism, Single Nucleotide/genetics
KW - Risk Factors
U2 - 10.1161/HYPERTENSIONAHA.111.00275
DO - 10.1161/HYPERTENSIONAHA.111.00275
M3 - SCORING: Journal article
C2 - 23478099
VL - 61
SP - 995
EP - 1001
JO - HYPERTENSION
JF - HYPERTENSION
SN - 0194-911X
IS - 5
ER -