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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1663-1678 |
| Number of pages | 16 |
| Journal | Human Molecular Genetics |
| Volume | 22 |
| Issue number | 8 |
| DOIs | |
| State | Published - Apr 1 2013 |
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ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Genetics(clinical)
Cite this
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; Baumert, Jens; Chang, Yen Pei Christy; Elbers, Clara C.; Farrall, Martin; Fischer, Mary E.; Franceschini, Nora; Gaunt, Tom R.; Gho, Johannes M.I.H.; Gieger, Christian; Gong, Yan; Isaacs, Aaron; Kleber, Marcus E.; Leach, Irene Mateo; McDonough, Caitrin W.; Meijs, Matthijs F.L.; Mellander, Olle; Molony, Cliona M.; Nolte, Ilja M.; Padmanabhan, Sandosh; Price, Tom S.; Rajagopalan, Ramakrishnan; Shaffer, Jonathan; Shah, Sonia; Shen, Haiqing; Soranzo, Nicole; van der Most, Peter J.; Van Iperen, Erik P.A.; Van Setten, Jessic A.; Vonk, Judith M.; Zhang, Li; Beitelshees, Amber L.; Berenson, Gerald S.; Bhatt, Deepak L.; Boer, Jolanda M.A.; Boerwinkle, Eric; Burkley, Ben; Burt, Amber; Chakravarti, Aravinda; Chen, Wei; Cooper-DeHoff, Rhonda M.; Curtis, Sean P.; Dreisbach, Albert; Duggan, David; Ehret, Georg B.; Fabsitz, Richard R.; Fornage, Myriam; Fox, Ervin; Furlong, Clement E.; Gansevoort, Ron T.; Hofker, Marten H.; Hovingh, G. Kees; Kirkland, Susan A.; Kottke-Marchant, Kandice; Kutlar, Abdullah; LaCroix, Andrea Z.; Langaee, Taimour Y.; Li, Yun R.; Lin, Honghuang; Liu, Kiang; Maiwald, Steffi; Malik, Rainer; Murugesan, Gurunathan; Newton-Cheh, Christopher; O'Connell, Jeffery R.; Onland-Moret, N. Charlotte; Ouwehand, Willem H.; Palmas, Walter; Penninx, Brenda W.; Pepine, Carl J.; Pettinger, Mary; Polak, Joseph F.; Ramachandran, Vasan S.; Ranchalis, Jane; Redline, Susan; Ridker, Paul M.; Rose, Lynda M.; Scharnag, Hubert; Schork, Nicholas J.; Shimbo, Daichi; Shuldiner, Alan R.; Srinivasan, Sathanur R.; Stolk, Ronald P.; Taylor, Herman A.; Thorand, Barbara; Trip, Mieke D.; van Duijn, Cornelia M.; Verschuren, W. Monique; Wijmenga, Cisca; Winkelmann, Bernhard R.; Wyatt, Sharon; Young, J. Hunter; Boehm, Bernhard O.; Caulfield, Mark J.; Chasman, Daniel I.; Davidson, Karina W.; Doevendans, Pieter A.; FitzGerald, Garret A.; Gums, John G.; Hakonarson, Hakon; Hillege, Hans L.; Illig, Thomas; Jarvik, Gail P.; Johnson, Julie A.; Kastelein, John J.P.; Koenig, Wolfgang; Study, Life Lines Cohort; März, Winfried; Mitchell, Braxton D.; Murray, Sarah S.; Oldehinkel, Albertine J.; Rader, Daniel J.; Reilly, Muredach P.; Reiner, Alex P.; Schadt, Eric E.; Silverstein, Roy L.; Snieder, Harold; Stanton, Alice V.; Uitterlinden, André G.; van der Harst, Pim; van der Schouw, Yvonne T.; Samani, Nilesh J.; Johnson, Andrew D.; Munroe, Patricia B.; de Bakker, Paul I.W.; Zhu, Xiaofeng; Levy, Daniel; Keating, Brendan J.; Asselbergs, Folkert W.
In: Human Molecular Genetics, Vol. 22, No. 8, 01.04.2013, p. 1663-1678.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Loci influencing blood pressure identified using a cardiovascular gene-centric array
AU - Ganesh, Santhi K.
AU - Tragante, Vinicius
AU - Guo, Wei
AU - Guo, Yiran
AU - Lanktree, Matthew B.
AU - Smith, Erin N.
AU - Johnson, Toby
AU - Castillo, Berta Almoguera
AU - Barnard, John
AU - Baumert, Jens
AU - Chang, Yen Pei Christy
AU - Elbers, Clara C.
AU - Farrall, Martin
AU - Fischer, Mary E.
AU - Franceschini, Nora
AU - Gaunt, Tom R.
AU - Gho, Johannes M.I.H.
AU - Gieger, Christian
AU - Gong, Yan
AU - Isaacs, Aaron
AU - Kleber, Marcus E.
AU - Leach, Irene Mateo
AU - McDonough, Caitrin W.
AU - Meijs, Matthijs F.L.
AU - Mellander, Olle
AU - Molony, Cliona M.
AU - Nolte, Ilja M.
AU - Padmanabhan, Sandosh
AU - Price, Tom S.
AU - Rajagopalan, Ramakrishnan
AU - Shaffer, Jonathan
AU - Shah, Sonia
AU - Shen, Haiqing
AU - Soranzo, Nicole
AU - van der Most, Peter J.
AU - Van Iperen, Erik P.A.
AU - Van Setten, Jessic A.
AU - Vonk, Judith M.
AU - Zhang, Li
AU - Beitelshees, Amber L.
AU - Berenson, Gerald S.
AU - Bhatt, Deepak L.
AU - Boer, Jolanda M.A.
AU - Boerwinkle, Eric
AU - Burkley, Ben
AU - Burt, Amber
AU - Chakravarti, Aravinda
AU - Chen, Wei
AU - Cooper-DeHoff, Rhonda M.
AU - Curtis, Sean P.
AU - Dreisbach, Albert
AU - Duggan, David
AU - Ehret, Georg B.
AU - Fabsitz, Richard R.
AU - Fornage, Myriam
AU - Fox, Ervin
AU - Furlong, Clement E.
AU - Gansevoort, Ron T.
AU - Hofker, Marten H.
AU - Hovingh, G. Kees
AU - Kirkland, Susan A.
AU - Kottke-Marchant, Kandice
AU - Kutlar, Abdullah
AU - LaCroix, Andrea Z.
AU - Langaee, Taimour Y.
AU - Li, Yun R.
AU - Lin, Honghuang
AU - Liu, Kiang
AU - Maiwald, Steffi
AU - Malik, Rainer
AU - Murugesan, Gurunathan
AU - Newton-Cheh, Christopher
AU - O'Connell, Jeffery R.
AU - Onland-Moret, N. Charlotte
AU - Ouwehand, Willem H.
AU - Palmas, Walter
AU - Penninx, Brenda W.
AU - Pepine, Carl J.
AU - Pettinger, Mary
AU - Polak, Joseph F.
AU - Ramachandran, Vasan S.
AU - Ranchalis, Jane
AU - Redline, Susan
AU - Ridker, Paul M.
AU - Rose, Lynda M.
AU - Scharnag, Hubert
AU - Schork, Nicholas J.
AU - Shimbo, Daichi
AU - Shuldiner, Alan R.
AU - Srinivasan, Sathanur R.
AU - Stolk, Ronald P.
AU - Taylor, Herman A.
AU - Thorand, Barbara
AU - Trip, Mieke D.
AU - van Duijn, Cornelia M.
AU - Verschuren, W. Monique
AU - Wijmenga, Cisca
AU - Winkelmann, Bernhard R.
AU - Wyatt, Sharon
AU - Young, J. Hunter
AU - Boehm, Bernhard O.
AU - Caulfield, Mark J.
AU - Chasman, Daniel I.
AU - Davidson, Karina W.
AU - Doevendans, Pieter A.
AU - FitzGerald, Garret A.
AU - Gums, John G.
AU - Hakonarson, Hakon
AU - Hillege, Hans L.
AU - Illig, Thomas
AU - Jarvik, Gail P.
AU - Johnson, Julie A.
AU - Kastelein, John J.P.
AU - Koenig, Wolfgang
AU - Study, Life Lines Cohort
AU - März, Winfried
AU - Mitchell, Braxton D.
AU - Murray, Sarah S.
AU - Oldehinkel, Albertine J.
AU - Rader, Daniel J.
AU - Reilly, Muredach P.
AU - Reiner, Alex P.
AU - Schadt, Eric E.
AU - Silverstein, Roy L.
AU - Snieder, Harold
AU - Stanton, Alice V.
AU - Uitterlinden, André G.
AU - van der Harst, Pim
AU - van der Schouw, Yvonne T.
AU - Samani, Nilesh J.
AU - Johnson, Andrew D.
AU - Munroe, Patricia B.
AU - de Bakker, Paul I.W.
AU - Zhu, Xiaofeng
AU - Levy, Daniel
AU - Keating, Brendan J.
AU - Asselbergs, Folkert W.
PY - 2013/4/1
Y1 - 2013/4/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84875781416&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84875781416&partnerID=8YFLogxK
U2 - 10.1093/hmg/dds555
DO - 10.1093/hmg/dds555
M3 - Article
C2 - 23303523
AN - SCOPUS:84875781416
VL - 22
SP - 1663
EP - 1678
JO - Human Molecular Genetics
JF - Human Molecular Genetics
SN - 0964-6906
IS - 8
ER -