| Literature DB >> 24560520 |
Vinicius Tragante1, Michael R Barnes2, Santhi K Ganesh3, Matthew B Lanktree4, Wei Guo5, Nora Franceschini6, Erin N Smith7, Toby Johnson8, Michael V Holmes9, Sandosh Padmanabhan10, Konrad J Karczewski11, Berta Almoguera12, John Barnard13, Jens Baumert14, Yen-Pei Christy Chang15, Clara C Elbers16, Martin Farrall17, Mary E Fischer18, Tom R Gaunt19, Johannes M I H Gho20, Christian Gieger21, Anuj Goel17, Yan Gong22, Aaron Isaacs23, Marcus E Kleber24, Irene Mateo Leach25, Caitrin W McDonough22, Matthijs F L Meijs20, Olle Melander26, Christopher P Nelson27, Ilja M Nolte28, Nathan Pankratz29, Tom S Price30, Jonathan Shaffer31, Sonia Shah32, Maciej Tomaszewski33, Peter J van der Most28, Erik P A Van Iperen34, Judith M Vonk28, Kate Witkowska8, Caroline O L Wong8, Li Zhang13, Amber L Beitelshees35, Gerald S Berenson36, Deepak L Bhatt37, Morris Brown38, Amber Burt39, Rhonda M Cooper-DeHoff22, John M Connell40, Karen J Cruickshanks41, Sean P Curtis42, George Davey-Smith19, Christian Delles43, Ron T Gansevoort44, Xiuqing Guo45, Shen Haiqing35, Claire E Hastie43, Marten H Hofker46, G Kees Hovingh47, Daniel S Kim48, Susan A Kirkland49, Barbara E Klein18, Ronald Klein18, Yun R Li12, Steffi Maiwald47, Christopher Newton-Cheh50, Eoin T O'Brien51, N Charlotte Onland-Moret16, Walter Palmas31, Afshin Parsa35, Brenda W Penninx52, Mary Pettinger53, Ramachandran S Vasan54, Jane E Ranchalis39, Paul M Ridker55, Lynda M Rose56, Peter Sever57, Daichi Shimbo31, Laura Steele9, Ronald P Stolk28, Barbara Thorand14, Mieke D Trip58, Cornelia M van Duijn23, W Monique Verschuren59, Cisca Wijmenga60, Sharon Wyatt61, J Hunter Young62, Aeilko H Zwinderman63, Connie R Bezzina64, Eric Boerwinkle65, Juan P Casas66, Mark J Caulfield8, Aravinda Chakravarti67, Daniel I Chasman55, Karina W Davidson68, Pieter A Doevendans20, Anna F Dominiczak10, Garret A FitzGerald69, John G Gums70, Myriam Fornage71, Hakon Hakonarson72, Indrani Halder73, Hans L Hillege25, Thomas Illig74, Gail P Jarvik57, Julie A Johnson22, John J P Kastelein47, Wolfgang Koenig75, Meena Kumari76, Winfried März77, Sarah S Murray78, Jeffery R O'Connell35, Albertine J Oldehinkel79, James S Pankow80, Daniel J Rader81, Susan Redline82, Muredach P Reilly81, Eric E Schadt83, Kandice Kottke-Marchant84, Harold Snieder28, Michael Snyder11, Alice V Stanton85, Martin D Tobin86, André G Uitterlinden87, Pim van der Harst88, Yvonne T van der Schouw89, Nilesh J Samani27, Hugh Watkins17, Andrew D Johnson90, Alex P Reiner53, Xiaofeng Zhu5, Paul I W de Bakker91, Daniel Levy92, Folkert W Asselbergs93, Patricia B Munroe94, Brendan J Keating95.
Abstract
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 < 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.Entities:
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Year: 2014 PMID： 24560520 PMCID： PMC3951943 DOI： 10.1016/j.ajhg.2013.12.016
Source DB: PubMed Journal: Am J Hum Genet ISSN： 0002-9297 Impact factor: 11.025