Gene-centric meta-analysis in 87,736 individuals of European ancestry identifies multiple blood-pressure-related loci

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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.

Original languageEnglish
Pages (from-to)349-60
Number of pages12
JournalAmerican Journal of Human Genetics
Issue number3
Publication statusPublished - 6 Mar 2014
Externally publishedYes


  • Arterial Pressure
  • Blood Pressure
  • Computational Biology/methods
  • Diastole
  • Europe
  • European Continental Ancestry Group/genetics
  • Genetic Loci
  • Genetics, Population
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Quality Control
  • Quantitative Trait Loci
  • Risk Factors
  • Systole


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