Genetic predisposition to higher blood pressure increases coronary artery disease risk

Wolfgang Lieb, Henning Jansen, Christina Loley, Michael J. Pencina, Christopher P. Nelson, Christopher Newton-Cheh, Sekar Kathiresan, Muredach P. Reilly, Themistocles L. Assimes, Eric Boerwinkle, Alistair S. Hall, Christian Hengstenberg, Reijo Laaksonen, Ruth McPherson, Unnur Thorsteinsdottir, Andreas Ziegler, Annette Peters, John R. Thompson, Inke R. König, Jeanette ErdmannNilesh J. Samani, Ramachandran S. Vasan, Heribert Schunkert

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

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). 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.

Original languageEnglish (US)
Pages (from-to)995-1001
Number of pages7
JournalHypertension
Volume61
Issue number5
DOIs
StatePublished - May 1 2013
Externally publishedYes

Keywords

  • blood pressure
  • coronary artery disease
  • genetics
  • polymorphism

ASJC Scopus subject areas

  • Internal Medicine

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