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., Padmanabhan, Sandosh, Karczewski, Konrad J., Almoguera, Berta, Barnard, John, Baumert, Jens, Chang, Yen-Pei Christy, Elbers, Clara C., Farrall, Martin, Fischer, Mary E., Gaunt, Tom R., Gho, Johannes M. I. H., Gieger, Christian, Goel, Anuj, Gong, Yan, Isaacs, Aaron, Kleber, Marcus E., Leach, Irene Mateo, McDonough, Caitrin W., Meijs, Matthijs F. L., Melander, Olle, Nelson, Christopher P., Nolte, Ilja M., Pankratz, Nathan, Price, Tom S., Shaffer, Jonathan, Shah, Sonia, Tomaszewski, Maciej, van der Most, Peter J., Van Iperen, Erik P. A., Vonk, Judith M., Witkowska, Kate, Wong, Caroline O. L., Zhang, Li, Beitelshees, Amber L., Berenson, Gerald S., Bhatt, Deepak L., Brown, Morris, Burt, Amber, Cooper-DeHoff, Rhonda M., Connell, John M., Cruickshanks, Karen J., Curtis, Sean P., Davey-Smith, George, Delles, Christian, Gansevoort, Ron T., Guo, Xiuqing, Haiqing, Shen, Hastie, Claire E., Hofker, Marten H., Hovingh, G. Kees, Kim, Daniel S., Kirkland, Susan A., Klein, Barbara E., Klein, Ronald, Li, Yun R., Maiwald, Steffi, Newton-Cheh, Christopher, O'Brien, Eoin T., Onland-Moret, N. Charlotte, Palmas, Walter, Parsa, Afshin, Penninx, Brenda W., Pettinger, Mary, Vasan, Ramachandran S., Ranchalis, Jane E., Ridker, Paul M., Rose, Lynda M., Sever, Peter, Shimbo, Daichi, Steele, Laura, Stolk, Ronald P., Thorand, Barbara, Trip, Mieke D., van Duijn, Cornelia M., Verschuren, W. Monique, Wijmenga, Cisca, Wyatt, Sharon, Young, J. Hunter, Zwinderman, Aeilko H., Bezzina, Connie R., Boerwinkle, Eric, Casas, Juan P., Caulfield, Mark J., Chakravarti, Aravinda, Chasman, Daniel I., Davidson, Karina W., Doevendans, Pieter A., Dominiczak, Anna F., FitzGerald, Garret A., Gums, John G., Fornage, Myriam, Hakonarson, Hakon, Halder, Indrani, Hillege, Hans L., Illig, Thomas, Jarvik, Gail P., Johnson, Julie A., Kastelein, John J. P., Koenig, Wolfgang, Kumari, Meena, Maerz, Winfried, Murray, Sarah S., O'Connell, Jeffery R., Oldehinkel, Albertine J., Pankow, James S., Rader, Daniel J., Redline, Susan, Reilly, Muredach P., Schadt, Eric E., Kottke-Marchant, Kandice, Snieder, Harold, Snyder, Michael, Stanton, Alice V., Tobin, Martin D., Uitterlinden, Andre G., van der Harst, Pim, van der Schouw, Yvonne T., Samani, Nilesh J., Watkins, Hugh, Johnson, Andrew D., Reiner, Alex P., Zhu, Xiaofeng, de Bakker, Paul I. W., Levy, Daniel, Asselbergs, Folkert W., Munroe, Patricia B. and Keating, Brendan J. (2014) Gene-centric meta-analysis in 87,736 individuals of European ancestry identifies multiple blood-pressure-related loci. American Journal of Human Genetics, 94 3: 349-360. doi:10.1016/j.ajhg.2013.12.016


Author Tragante, Vinicius
Barnes, Michael R.
Ganesh, Santhi K.
Lanktree, Matthew B.
Guo, Wei
Franceschini, Nora
Smith, Erin N.
Johnson, Toby
Holmes, Michael V.
Padmanabhan, Sandosh
Karczewski, Konrad J.
Almoguera, Berta
Barnard, John
Baumert, Jens
Chang, Yen-Pei Christy
Elbers, Clara C.
Farrall, Martin
Fischer, Mary E.
Gaunt, Tom R.
Gho, Johannes M. I. H.
Gieger, Christian
Goel, Anuj
Gong, Yan
Isaacs, Aaron
Kleber, Marcus E.
Leach, Irene Mateo
McDonough, Caitrin W.
Meijs, Matthijs F. L.
Melander, Olle
Nelson, Christopher P.
Nolte, Ilja M.
Pankratz, Nathan
Price, Tom S.
Shaffer, Jonathan
Shah, Sonia
Tomaszewski, Maciej
van der Most, Peter J.
Van Iperen, Erik P. A.
Vonk, Judith M.
Witkowska, Kate
Wong, Caroline O. L.
Zhang, Li
Beitelshees, Amber L.
Berenson, Gerald S.
Bhatt, Deepak L.
Brown, Morris
Burt, Amber
Cooper-DeHoff, Rhonda M.
Connell, John M.
Cruickshanks, Karen J.
Curtis, Sean P.
Davey-Smith, George
Delles, Christian
Gansevoort, Ron T.
Guo, Xiuqing
Haiqing, Shen
Hastie, Claire E.
Hofker, Marten H.
Hovingh, G. Kees
Kim, Daniel S.
Kirkland, Susan A.
Klein, Barbara E.
Klein, Ronald
Li, Yun R.
Maiwald, Steffi
Newton-Cheh, Christopher
O'Brien, Eoin T.
Onland-Moret, N. Charlotte
Palmas, Walter
Parsa, Afshin
Penninx, Brenda W.
Pettinger, Mary
Vasan, Ramachandran S.
Ranchalis, Jane E.
Ridker, Paul M.
Rose, Lynda M.
Sever, Peter
Shimbo, Daichi
Steele, Laura
Stolk, Ronald P.
Thorand, Barbara
Trip, Mieke D.
van Duijn, Cornelia M.
Verschuren, W. Monique
Wijmenga, Cisca
Wyatt, Sharon
Young, J. Hunter
Zwinderman, Aeilko H.
Bezzina, Connie R.
Boerwinkle, Eric
Casas, Juan P.
Caulfield, Mark J.
Chakravarti, Aravinda
Chasman, Daniel I.
Davidson, Karina W.
Doevendans, Pieter A.
Dominiczak, Anna F.
FitzGerald, Garret A.
Gums, John G.
Fornage, Myriam
Hakonarson, Hakon
Halder, Indrani
Hillege, Hans L.
Illig, Thomas
Jarvik, Gail P.
Johnson, Julie A.
Kastelein, John J. P.
Koenig, Wolfgang
Kumari, Meena
Maerz, Winfried
Murray, Sarah S.
O'Connell, Jeffery R.
Oldehinkel, Albertine J.
Pankow, James S.
Rader, Daniel J.
Redline, Susan
Reilly, Muredach P.
Schadt, Eric E.
Kottke-Marchant, Kandice
Snieder, Harold
Snyder, Michael
Stanton, Alice V.
Tobin, Martin D.
Uitterlinden, Andre G.
van der Harst, Pim
van der Schouw, Yvonne T.
Samani, Nilesh J.
Watkins, Hugh
Johnson, Andrew D.
Reiner, Alex P.
Zhu, Xiaofeng
de Bakker, Paul I. W.
Levy, Daniel
Asselbergs, Folkert W.
Munroe, Patricia B.
Keating, Brendan J.
Title Gene-centric meta-analysis in 87,736 individuals of European ancestry identifies multiple blood-pressure-related loci
Journal name American Journal of Human Genetics   Check publisher's open access policy
ISSN 0002-9297
1537-6605
Publication date 2014-03
Year available 2014
Sub-type Article (original research)
DOI 10.1016/j.ajhg.2013.12.016
Open Access Status DOI
Volume 94
Issue 3
Start page 349
End page 360
Total pages 12
Place of publication Cambridge, United States
Publisher Cell Press
Collection year 2015
Language eng
Formatted 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.
Keyword Genomewide association
Coronary-artery-disease
Human prefrontal cortex
Factor-Kappa-B
Essential-hypertension
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
Queensland Brain Institute Publications
 
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