UP - logo
E-viri
Recenzirano Odprti dostop
  • Genetic predisposition to h...
    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

    Hypertension 61, Številka: 5
    Journal Article

    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.