Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure

Louise V. Wain, Germaine C. Verwoert, Paul F. O'Reilly, Gang Shi, Toby Johnson, Andrew D. Johnson, Murielle Bochud, Kenneth M. Rice, Peter Henneman, Albert V. Smith, Georg B. Ehret, Najaf Amin, Martin G. Larson, Vincent Mooser, David Hadley, Marcus Doerr, Joshua C. Bis, Thor Aspelund, Tonu Esko, A. Cecile J. W. JanssensJing Hua Zhao, Simon Heath, Maris Laan, Jingyuan Fu, Giorgio Pistis, Jian'an Luan, Pankaj Arora, Gavin Lucas, Nicola Pirastu, Irene Pichler, Anne U. Jackson, Rebecca J. Webster, Feng Zhang, John F. Peden, Helena Schmidt, Toshiko Tanaka, Harry Campbell, Wilmar Igl, Yuri Milaneschi, Jouke-Jan Hottenga, Veronique Vitart, Daniel I. Chasman, Stella Trompet, Jennifer L. Bragg-Gresham, Behrooz Z. Alizadeh, Ilja M. Nolte, Melanie M. van der Klauw, Ronald P. Stolk, Harold Snieder, Ko Willems van Dijk, Lifelines Cohort Study, EchoGen Consortium, AortaGen Consortium, CHARGE Consortium Heart Failure, KidneyGen Consortium, CKDGen Consortium, Cardiogenics Consortium, CARDIOGRAM

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Abstract

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans(1-3). We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 x 10(-8) to P = 2.3 x 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP.

Original languageEnglish
Pages (from-to)1005-U122
Number of pages8
JournalNature Genetics
Volume43
Issue number10
DOIs
Publication statusPublished - Oct-2011

Keywords

  • ADRENERGIC-RECEPTOR TRAFFICKING
  • CARDIOVASCULAR-DISEASE RISK
  • BLOOD-PRESSURE
  • HEART-FAILURE
  • HYPERTENSION
  • METAANALYSIS
  • MORTALITY
  • GENE
  • MICE
  • RELEVANCE

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