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Loci influencing blood pressure identified using a cardiovascular gene-centric array

Ganesh, Santhi K.; Tragante, Vinicius; Guo, Wei; Guo, Yiran; Lanktree, Matthew B.; Smith, Erin N.; Johnson, Toby; Castillo, Berta Almoguera; Barnard, John and Baumert, Jens, et al. (2013) In Human Molecular Genetics 22(8). p.1663-1678
Abstract
Blood pressure (BP) is a heritable determinant of risk for cardiovascular disease (CVD). To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP), we genotyped 50 000 single-nucleotide polymorphisms (SNPs) that capture variation in 2100 candidate genes for cardiovascular phenotypes in 61 619 individuals of European ancestry from cohort studies in the USA and Europe. We identified novel associations between rs347591 and SBP (chromosome 3p25.3, in an intron of HRH1) and between rs2169137 and DBP (chromosome1q32.1 in an intron of MDM4) and between rs2014408 and SBP (chromosome 11p15 in an intron of SOX6), previously reported to be associated with MAP. We also... (More)
Blood pressure (BP) is a heritable determinant of risk for cardiovascular disease (CVD). To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP), we genotyped 50 000 single-nucleotide polymorphisms (SNPs) that capture variation in 2100 candidate genes for cardiovascular phenotypes in 61 619 individuals of European ancestry from cohort studies in the USA and Europe. We identified novel associations between rs347591 and SBP (chromosome 3p25.3, in an intron of HRH1) and between rs2169137 and DBP (chromosome1q32.1 in an intron of MDM4) and between rs2014408 and SBP (chromosome 11p15 in an intron of SOX6), previously reported to be associated with MAP. We also confirmed 10 previously known loci associated with SBP, DBP, MAP or PP (ADRB1, ATP2B1, SH2B3/ATXN2, CSK, CYP17A1, FURIN, HFE, LSP1, MTHFR, SOX6) at array-wide significance (P 2.4 10(6)). We then replicated these associations in an independent set of 65 886 individuals of European ancestry. The findings from expression QTL (eQTL) analysis showed associations of SNPs in the MDM4 region with MDM4 expression. We did not find any evidence of association of the two novel SNPs in MDM4 and HRH1 with sequelae of high BP including coronary artery disease (CAD), left ventricular hypertrophy (LVH) or stroke. In summary, we identified two novel loci associated with BP and confirmed multiple previously reported associations. Our findings extend our understanding of genes involved in BP regulation, some of which may eventually provide new targets for therapeutic intervention. (Less)
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Human Molecular Genetics
volume
22
issue
8
pages
1663 - 1678
publisher
Oxford University Press
external identifiers
  • wos:000316965400016
  • scopus:84875781416
ISSN
0964-6906
DOI
10.1093/hmg/dds555
language
English
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yes
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2273fe6e-736b-43fe-865b-390c202bf114 (old id 3748324)
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2013-06-03 08:35:46
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2019-01-06 04:45:59
@article{2273fe6e-736b-43fe-865b-390c202bf114,
  abstract     = {Blood pressure (BP) is a heritable determinant of risk for cardiovascular disease (CVD). To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP), we genotyped 50 000 single-nucleotide polymorphisms (SNPs) that capture variation in 2100 candidate genes for cardiovascular phenotypes in 61 619 individuals of European ancestry from cohort studies in the USA and Europe. We identified novel associations between rs347591 and SBP (chromosome 3p25.3, in an intron of HRH1) and between rs2169137 and DBP (chromosome1q32.1 in an intron of MDM4) and between rs2014408 and SBP (chromosome 11p15 in an intron of SOX6), previously reported to be associated with MAP. We also confirmed 10 previously known loci associated with SBP, DBP, MAP or PP (ADRB1, ATP2B1, SH2B3/ATXN2, CSK, CYP17A1, FURIN, HFE, LSP1, MTHFR, SOX6) at array-wide significance (P 2.4 10(6)). We then replicated these associations in an independent set of 65 886 individuals of European ancestry. The findings from expression QTL (eQTL) analysis showed associations of SNPs in the MDM4 region with MDM4 expression. We did not find any evidence of association of the two novel SNPs in MDM4 and HRH1 with sequelae of high BP including coronary artery disease (CAD), left ventricular hypertrophy (LVH) or stroke. In summary, we identified two novel loci associated with BP and confirmed multiple previously reported associations. Our findings extend our understanding of genes involved in BP regulation, some of which may eventually provide new targets for therapeutic intervention.},
  author       = {Ganesh, Santhi K. and Tragante, Vinicius and Guo, Wei and Guo, Yiran and Lanktree, Matthew B. and Smith, Erin N. and Johnson, Toby and Castillo, Berta Almoguera and Barnard, John and Baumert, Jens and Chang, Yen-Pei Christy and Elbers, Clara C. and Farrall, Martin and Fischer, Mary E. and Franceschini, Nora and Gaunt, Tom R. and Gho, Johannes M. I. H. and Gieger, Christian 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 Molony, Cliona M. and Nolte, Ilja M. and Padmanabhan, Sandosh and Price, Tom S. and Rajagopalan, Ramakrishnan and Shaffer, Jonathan and Shah, Sonia and Shen, Haiqing and Soranzo, Nicole and van der Most, Peter J. and Van Iperen, Erik P. A. and Van Setten, Jessic A. and Vonk, Judith M. and Zhang, Li and Beitelshees, Amber L. and Berenson, Gerald S. and Bhatt, Deepak L. and Boer, Jolanda M. A. and Boerwinkle, Eric and Burkley, Ben and Burt, Amber and Chakravarti, Aravinda and Chen, Wei and Cooper-DeHoff, Rhonda M. and Curtis, Sean P. and Dreisbach, Albert and Duggan, David and Ehret, Georg B. and Fabsitz, Richard R. and Fornage, Myriam and Fox, Ervin and Furlong, Clement E. and Gansevoort, Ron T. and Hofker, Marten H. and Hovingh, G. Kees and Kirkland, Susan A. and Kottke-Marchant, Kandice and Kutlar, Abdullah and LaCroix, Andrea Z. and Langaee, Taimour Y. and Li, Yun R. and Lin, Honghuang and Liu, Kiang and Maiwald, Steffi and Malik, Rainer and Murugesan, Gurunathan and Newton-Cheh, Christopher and OConnell, Jeffery R. and Onland-Moret, N. Charlotte and Ouwehand, Willem H. and Palmas, Walter and Penninx, Brenda W. and Pepine, Carl J. and Pettinger, Mary and Polak, Joseph F. and Ramachandran, Vasan S. and Ranchalis, Jane and Redline, Susan and Ridker, Paul M. and Rose, Lynda M. and Scharnag, Hubert and Schork, Nicholas J. and Shimbo, Daichi and Shuldiner, Alan R. and Srinivasan, Sathanur R. and Stolk, Ronald P. and Taylor, Herman A. and Thorand, Barbara and Trip, Mieke D. and van Duijn, Cornelia M. and Verschuren, W. Monique and Wijmenga, Cisca and Winkelmann, Bernhard R. and Wyatt, Sharon and Young, J. Hunter and Boehm, Bernhard O. and Caulfield, Mark J. and Chasman, Daniel I. and Davidson, Karina W. and Doevendans, Pieter A. and FitzGerald, Garret A. and Gums, John G. and Hakonarson, Hakon and Hillege, Hans L. and Illig, Thomas and Jarvik, Gail P. and Johnson, Julie A. and Kastelein, John J. P. and Koenig, Wolfgang and Maerz, Winfried and Mitchell, Braxton D. and Murray, Sarah S. and Oldehinkel, Albertine J. and Rader, Daniel J. and Reilly, Muredach P. and Reiner, Alex P. and Schadt, Eric E. and Silverstein, Roy L. and Snieder, Harold and Stanton, Alice V. and Uitterlinden, Andre G. and van der Harst, Pim and van der Schouw, Yvonne T. and Samani, Nilesh J. and Johnson, Andrew D. and Munroe, Patricia B. and de Bakker, Paul I. W. and Zhu, Xiaofeng and Levy, Daniel and Keating, Brendan J. and Asselbergs, Folkert W.},
  issn         = {0964-6906},
  language     = {eng},
  number       = {8},
  pages        = {1663--1678},
  publisher    = {Oxford University Press},
  series       = {Human Molecular Genetics},
  title        = {Loci influencing blood pressure identified using a cardiovascular gene-centric array},
  url          = {http://dx.doi.org/10.1093/hmg/dds555},
  volume       = {22},
  year         = {2013},
}