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Gene-centric Meta-analysis in 87,736 Individuals of European Ancestry Identifies Multiple Blood-Pressure-Related Loci.

Tragante, Vinicius; Barnes, Michael R; Ganesh, Santhi K; Lanktree, Matthew B; Guo, Wei; Franceschini, Nora; Smith, Erin N; Johnson, Toby; Holmes, Michael V and Padmanabhan, Sandosh, et al. (2014) In American Journal of Human Genetics 94(3). p.349-360
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.... (More)
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. (Less)
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American Journal of Human Genetics
volume
94
issue
3
pages
349 - 360
publisher
Cell Press
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  • pmid:24560520
  • wos:000332611400009
  • scopus:84895920262
ISSN
0002-9297
DOI
10.1016/j.ajhg.2013.12.016
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English
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9ff78ce1-5738-4c31-8c05-df340032750d (old id 4334154)
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http://www.ncbi.nlm.nih.gov/pubmed/24560520?dopt=Abstract
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2014-03-05 20:02:49
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@article{9ff78ce1-5738-4c31-8c05-df340032750d,
  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 &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.},
  author       = {Tragante, Vinicius and Barnes, Michael R and Ganesh, Santhi K and Lanktree, Matthew B and Guo, Wei and Franceschini, Nora and Smith, Erin N and Johnson, Toby and Holmes, Michael V and Padmanabhan, Sandosh and Karczewski, Konrad J and Almoguera, Berta and Barnard, John and Baumert, Jens and Chang, Yen-Pei Christy and Elbers, Clara C and Farrall, Martin and Fischer, Mary E and Gaunt, Tom R and Gho, Johannes M I H and Gieger, Christian and Goel, Anuj and Gong, Yan and Isaacs, Aaron and Kleber, Marcus E and Leach, Irene Mateo and McDonough, Caitrin W and Meijs, Matthijs F L and Melander, Olle and Nelson, Christopher P and Nolte, Ilja M and Pankratz, Nathan and Price, Tom S and Shaffer, Jonathan and Shah, Sonia and Tomaszewski, Maciej and van der Most, Peter J and Van Iperen, Erik P A and Vonk, Judith M and Witkowska, Kate and Wong, Caroline O L and Zhang, Li and Beitelshees, Amber L and Berenson, Gerald S and Bhatt, Deepak L and Brown, Morris and Burt, Amber and Cooper-Dehoff, Rhonda M and Connell, John M and Cruickshanks, Karen J and Curtis, Sean P and Davey-Smith, George and Delles, Christian and Gansevoort, Ron T and Guo, Xiuqing and Haiqing, Shen and Hastie, Claire E and Hofker, Marten H and Hovingh, G Kees and Kim, Daniel S and Kirkland, Susan A and Klein, Barbara E and Klein, Ronald and Li, Yun R and Maiwald, Steffi and Newton-Cheh, Christopher and O'Brien, Eoin T and Onland-Moret, N Charlotte and Palmas, Walter and Parsa, Afshin and Penninx, Brenda W and Pettinger, Mary and Vasan, Ramachandran S and Ranchalis, Jane E and M Ridker, Paul and Rose, Lynda M and Sever, Peter and Shimbo, Daichi and Steele, Laura and Stolk, Ronald P and Thorand, Barbara and Trip, Mieke D and van Duijn, Cornelia M and Verschuren, W Monique and Wijmenga, Cisca and Wyatt, Sharon and Young, J Hunter and Zwinderman, Aeilko H and Bezzina, Connie R and Boerwinkle, Eric and Casas, Juan P and Caulfield, Mark J and Chakravarti, Aravinda and Chasman, Daniel I and Davidson, Karina W and Doevendans, Pieter A and Dominiczak, Anna F and Fitzgerald, Garret A and Gums, John G and Fornage, Myriam and Hakonarson, Hakon and Halder, Indrani and Hillege, Hans L and Illig, Thomas and Jarvik, Gail P and Johnson, Julie A and Kastelein, John J P and Koenig, Wolfgang and Kumari, Meena and März, Winfried and Murray, Sarah S and O'Connell, Jeffery R and Oldehinkel, Albertine J and Pankow, James S and Rader, Daniel J and Redline, Susan and Reilly, Muredach P and Schadt, Eric E and Kottke-Marchant, Kandice and Snieder, Harold and Snyder, Michael and Stanton, Alice V and Tobin, Martin D and Uitterlinden, André G and van der Harst, Pim and van der Schouw, Yvonne T and Samani, Nilesh J and Watkins, Hugh and Johnson, Andrew D and Reiner, Alex P and Zhu, Xiaofeng and de Bakker, Paul I W and Levy, Daniel and Asselbergs, Folkert W and Munroe, Patricia B and Keating, Brendan J},
  issn         = {0002-9297},
  language     = {eng},
  number       = {3},
  pages        = {349--360},
  publisher    = {Cell Press},
  series       = {American Journal of Human Genetics},
  title        = {Gene-centric Meta-analysis in 87,736 Individuals of European Ancestry Identifies Multiple Blood-Pressure-Related Loci.},
  url          = {http://dx.doi.org/10.1016/j.ajhg.2013.12.016},
  volume       = {94},
  year         = {2014},
}