Gene-centric Meta-analysis in 87,736 Individuals of European Ancestry Identifies Multiple Blood-Pressure-Related Loci
Creators: name: Tragante, Vinicius
name: Barnes, Michael R.
name: Ganesh, Santhi K.
name: Lanktree, Matthew B.
name: Guo, Wei
name: Franceschini, Nora
name: Smith, Erin N.
name: Johnson, Toby
name: Holmes, Michael V.
name: Padmanabhan, Sandosh
name: Karczewski, Konrad J.
name: Almoguera, Berta
name: Barnard, John
name: Baumert, Jens
name: Chang, Yen-Pei Christy
name: Elbers, Clara C.
name: Farrall, Martin
name: Fischer, Mary E.
name: Gaunt, Tom R.
name: Gho, Johannes M. I. H.
name: Gieger, Christian
name: Goel, Anuj
name: Gong, Yan
name: Isaacs, Aaron
name: Kleber, Marcus E.
name: Leach, Irene Mateo
name: McDonough, Caitrin W.
name: Meijs, Matthijs F. L.
name: Melander, Olle
name: Nelson, Christopher P.
name: Nolte, Ilja M.
name: Pankratz, Nathan
name: Price, Tom S.
name: Shaffer, Jonathan
name: Shah, Sonia
name: Tomaszewski, Maciej
name: Van Der Most, Peter J.
name: Van Iperen, Erik P. A.
name: Vonk, Judith M.
name: Witkowska, Kate
name: Wong, Caroline O. L.
name: Zhang, Li
name: Beitelshees, Amber L.
name: Berenson, Gerald S.
name: Bhatt, Deepak L.
name: Brown, Morris
name: Burt, Amber
name: Cooper-DeHoff, Rhonda M.
name: Connell, John M.
name: Cruickshanks, Karen J.
name: Curtis, Sean P.
name: Davey-Smith, George
name: Delles, Christian
name: Gansevoort, Ron T.
name: Guo, Xiuqing
name: Haiqing, Shen
name: Hastie, Claire E.
name: Hofker, Marten H.
name: Hovingh, G. Kees
name: Kim, Daniel S.
name: Kirkland, Susan A.
name: Klein, Barbara E.
name: Klein, Ronald
name: Li, Yun R.
name: Maiwald, Steffi
name: Newton-Cheh, Christopher
name: O’Brien, Eoin T.
name: Onland-Moret, N. Charlotte
name: Palmas, Walter R.
name: Parsa, Afshin
name: Penninx, Brenda W.
name: Pettinger, Mary
name: Vasan, Ramachandran S.
name: Ranchalis, Jane E.
name: Ridker, Paul M.
name: Rose, Lynda M.
name: Sever, Peter
name: Shimbo, Daichi
name: Steele, Laura
name: Stolk, Ronald P.
name: Thorand, Barbara
name: Trip, Mieke D.
name: Van Duijn, Cornelia M.
name: Verschuren, W. Monique
name: Wijmenga, Cisca
name: Wyatt, Sharon
name: Young, J. Hunter
name: Zwinderman, Aeilko H.
name: Bezzina, Connie R.
name: Boerwinkle, Eric
name: Casas, Juan P.
name: Caulfield, Mark J.
name: Chakravarti, Aravinda
name: Chasman, Daniel I.
name: Davidson, Karina W.
name: Doevendans, Pieter A.
name: Dominiczak, Anna F.
name: FitzGerald, Garret A.
name: Gums, John G.
name: Fornage, Myriam
name: Hakonarson, Hakon
name: Halder, Indrani
name: Hillege, Hans L.
name: Illig, Thomas
name: Jarvik, Gail P.
name: Johnson, Julie A.
name: Kastelein, John J. P.
name: Koenig, Wolfgang
name: Kumari, Meena
name: Marz, Winfried
name: Murray, Sarah S.
name: O’Connell, Jeffrey R.
name: Oldehinkel, Albertine J.
name: Pankow, James S.
name: Rader, Daniel J.
name: Redline, Susan
name: Reilly, Muredach P.
name: Schadt, Eric E.
name: Kottke-Marchant, Kandice
name: Snieder, Harold
name: Snyder, Michael
name: Stanton, Alice V.
name: Tobin, Martin D.
name: Uitterlinden, Andre G.
name: Van Der Harst, Pim
name: Van Der Schouw, Yvonne T.
name: Samani, Nilesh J.
name: Watkins, Hugh
name: Johnson, Andrew D.
name: Reiner, Alex P.
name: Zhu, Xiaofeng
name: De Bakker, Paul I. W.
name: Levy, Daniel
name: Asselbergs, Folkert W.
name: Munroe, Patricia B.
name: Keating, Brendan J.
Publisher: name: Columbia University
Year: 2014
Subjects: subject: Blood pressure
subject: Human genetics--Research
subject: Meta-analysis
subject: Epidemiology
subject: Genetics
subject: FOS: Biological sciences
subject: Molecular biology

description: Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ∼50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p &lt; 6 × 10−7) and confirmed 27 previously reported associations. Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2. Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules. In summary, we identified previously unknown loci associated with BP. Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification.