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
PY - 2013/5/1
Y1 - 2013/5/1
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). 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). 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). 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). 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.
UR - http://www.scopus.com/inward/record.url?scp=84876677420&partnerID=8YFLogxK
U2 - 10.1161/HYPERTENSIONAHA.111.00275
DO - 10.1161/HYPERTENSIONAHA.111.00275
M3 - Journal articles
AN - SCOPUS:84876677420
SN - 0194-911X
VL - 61
SP - 995
EP - 1001
JO - Hypertension
JF - Hypertension
IS - 5
ER -