Loci influencing blood pressure identified using a cardiovascular gene-centric array
Creators: name: Ganesh, Santhi K.
name: Tragante, Vinicius
name: Guo, Wei
name: Guo, Yiran
name: Lanktree, Matthew B.
name: Smith, Erin N.
name: Johnson, Toby
name: Almoguera Castillo, Berta
name: Barnard, John
name: Baumer, Jens
name: Chang, Yen-Pei Christy
name: Elbers, Clara C.
name: Farrall, Martin
name: Fischer, Mary E.
name: Franceschini, Nora
name: Gaunt, Tom R.
name: Gho, Johannes M. I. H.
name: Gieger, Christian
name: Gong, Yan
name: Isaacs, Aaron
name: Kleber, Marcus E.
name: Leach, Irene Mateo
name: McDonough, Caitrin W.
name: Meijs, Matthijs F. L.
name: Mellander, Olle
name: Molony, Cliona M.
name: Nolte, Ilja M.
name: Padmanabhan, Sandosh
name: Price, Tom S.
name: Rajagopalan, Ramakrishnan
name: Shaffer, Jonathan
name: Shah, Sonia
name: Shen, Haiqing
name: Soranzo, Nicole
name: Van Der Most, Peter J.
name: Van Iperen, Erik P. A.
name: Van Setten, Jessic A.
name: Vonk, Judith M.
name: Zhang, Li
name: Beitelshees, Amber L.
name: Berenson, Gerald S.
name: Bhatt, Deepak L.
name: Boer, Jolanda M. A.
name: Boerwinkle, Eric
name: Burkley, Ben
name: Burt, Amber
name: Chakravarti, Aravinda
name: Chen, Wei
name: Cooper-DeHoff, Rhonda M.
name: Curtis, Sean P.
name: Dreisbach, Albert
name: Duggan, David
name: Ehret, Georg B.
name: Fabsitz, Richard R.
name: Fornage, Myriam
name: Fox, Ervin
name: Furlong, Clement E.
name: Gansevoort, Ron T.
name: Hofker, Marten H.
name: Hovingh, G. Kees
name: Kirkland, Susan A.
name: Kutlar, Abdullah
name: Kottke-Marchant, Kandice
name: LaCroix, Andrea Z.
name: Langaee, Taimour Y.
name: Li, Yun R.
name: Lin, Honghuang
name: Liu, Kiang
name: Maiwald, Steffi
name: Malik, Rainer
name: Murugesan, Gurunathan
name: Newton-Cheh, Christopher
name: O’Connell, Jeffery R.
name: Onland-Moret, N. Charlotte
name: Ouwehand, Willem H.
name: Palmas, Walter R.
name: Penninx, Brenda W.
name: Pepine, Carl J.
name: Pettinger, Mary
name: Polak, Joseph F.
name: Ramachandran, Vasan S.
name: Ranchalis, Jane
name: Redline, Susan
name: Ridker, Paul M.
name: Rose, Lynda M.
name: Scharnag, Hubert
name: Schork, Nicholas J.
name: Shimbo, Daichi
name: Shuldiner, Alan R.
name: Srinivasan, Sathanur R.
name: Stolk, Ronald P.
name: Taylor, Herman A.
name: Thorand, Barbara
name: Trip, Mieke D.
name: Van Duijn, Cornelia M.
name: Verschuren, W. Monique
name: Wijmenga, Cisca
name: Winkelmann, Bernhard R.
name: Wyatt, Sharon
name: Young, J. Hunter
name: Boehm, Bernhard O.
name: Caulfield, Mark J.
name: Chasman, Daniel I.
name: Davidson, Karina W.
name: Doevendans, Pieter A.
name: FitzGerald, Garret A.
name: Gums, John G.
name: Hakonarson, Hakon
name: Hillege, Hans L.
name: Illig, Thomas
name: Jarvik, Gail P.
name: Johnson, Julie A.
name: Kastelein, John J. P.
name: Koenig, Wolfgang
name: Marz, Winfried
name: Mitchell, Braxton D.
name: Murray, Sarah S.
name: Oldehinkel, Albertine J.
name: Rader, Daniel J.
name: Reilly, Muredach P.
name: Reiner, Alex P.
name: Schadt, Eric E.
name: Silverstein, Roy L.
name: Snieder, Harold
name: Stanton, Alice V.
name: Uitterlinden, Andre G.
name: Van Der Harst, Pim
name: Van Der Schouw, Yvonne T.
name: Samani, Nilesh J.
name: Johnson, Andrew D.
name: Munroe, Patricia B.
name: De Bakker, Paul I. W.
name: Zhu, Xiaofeng
name: Levy, Daniel
name: Keating, Brendan J.
name: Asselbergs, Folkert W.
name: CARDIOGRAM
name: METASTROKE
name: LifeLines Cohort Study
Publisher: name: Columbia University
Year: 2013
Subjects: Human genetics
Blood pressure
Blood pressure--Regulation
Medical sciences
Molecular biology

description: Blood pressure (BP) is a heritable determinant of risk for cardiovascular disease (CVD). To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP), we genotyped ∼50 000 single-nucleotide polymorphisms (SNPs) that capture variation in ∼2100 candidate genes for cardiovascular phenotypes in 61 619 individuals of European ancestry from cohort studies in the USA and Europe. We identified novel associations between rs347591 and SBP (chromosome 3p25.3, in an intron of HRH1) and between rs2169137 and DBP (chromosome1q32.1 in an intron of MDM4) and between rs2014408 and SBP (chromosome 11p15 in an intron of SOX6), previously reported to be associated with MAP. We also confirmed 10 previously known loci associated with SBP, DBP, MAP or PP (ADRB1, ATP2B1, SH2B3/ATXN2, CSK, CYP17A1, FURIN, HFE, LSP1, MTHFR, SOX6) at array-wide significance (P &lt; 2.4 × 10−6). We then replicated these associations in an independent set of 65 886 individuals of European ancestry. The findings from expression QTL (eQTL) analysis showed associations of SNPs in the MDM4 region with MDM4 expression. We did not find any evidence of association of the two novel SNPs in MDM4 and HRH1 with sequelae of high BP including coronary artery disease (CAD), left ventricular hypertrophy (LVH) or stroke. In summary, we identified two novel loci associated with BP and confirmed multiple previously reported associations. Our findings extend our understanding of genes involved in BP regulation, some of which may eventually provide new targets for therapeutic intervention.