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Ganesh, S.K.* ; Tragante, V.* ; Guo, W.* ; Guo, Y.* ; Lanktree, M.B.* ; Smith, E.N.* ; Johnson, T.* ; Castillo, B.A.* ; Barnard, J.* ; Baumert, J.J. ; Chang, Y.P.* ; Elbers, C.C.* ; Farrall, M.* ; Fischer, M.E.* ; Franceschini, N.* ; Gaunt, T.R.* ; Gho, J.M.* ; Gieger, C. ; Gong, Y.* ; Isaacs, A.* ; Kleber, M.E.* ; Mateo Leach, I.* ; McDonough, C.W.* ; Meijs, M.F.* ; Mellander, O.* ; Molony, C.M.* ; Nolte, I.M.* ; Padmanabhan, S.* ; Price, T.S.* ; Rajagopalan, R.* ; Shaffer, J.* ; Shah, S.* ; Shen, H.* ; Soranzo, N.* ; van der Most, P.J.* ; van Iperen, E.P.* ; van Setten, J.A.* ; Vonk, J.M.* ; Zhang, L.* ; Beitelshees, A.L.* ; Berenson, G.S.* ; Bhatt, D.L.* ; Boer, J.M.* ; Boerwinkle, E.* ; Burkley, B.* ; Burt, A.* ; Chakravarti, A.* ; Chen, W.* ; Cooper-DeHoff, R.M.* ; Curtis, S.P.* ; Dreisbach, A.* ; Duggan, D.* ; Ehret, G.B.* ; Fabsitz, R.R.* ; Fornage, M.* ; Fox, E.* ; Furlong, C.E.* ; Gansevoort, R.T.* ; Hofker, M.H.* ; Hovingh, G.K.* ; Kirkland, S.A.* ; Kottke-Marchant, K.* ; Kutlar, A.* ; LaCroix, A.Z.* ; Langaee, T.Y.* ; Li, Y.R.* ; Lin, H.* ; Liu, K.* ; Maiwald, S.* ; Malik, R.* ; CARDIoGRAM Consortium (Illig, T. ; Meisinger, C. ; Meitinger, T. ; Peters, A. ; Döring, A. ; Klopp, N. ; Wichmann, H.-E.) ; METASTROKE Consortium (*) ; Murugesan, G.* ; Newton-Cheh, C.* ; O'Connell, J.R.* ; Onland-Moret, N.C.* ; Ouwehand, W.H.* ; Palmas, W.* ; Penninx, B.W.* ; Pepine, C.J.* ; Pettinger, M.* ; Polak, J.F.* ; Ramachandran, V.S.* ; Ranchalis, J.* ; Redline, S.* ; Ridker, P.M.* ; Rose, L.M.* ; Scharnag, H.* ; Schork, N.J.* ; Shimbo, D.* ; Shuldiner, A.R.* ; Srinivasan, S.R.* ; Stolk, R.P.* ; Taylor, H.A.* ; Thorand, B. ; Trip, M.D.* ; van Duijn, C.M.* ; Verschuren, W.M.* ; Wijmenga, C.* ; Winkelmann, B.R.* ; Wyatt, S.* ; Young, J.H.* ; Boehm, B.O.* ; Caulfield, M.J.* ; Chasman, D.I.* ; Davidson, K.W.* ; Doevendans, P.A.* ; Fitzgerald, G.A.* ; Gums, J.G.* ; Hakonarson, H.* ; Hillege, H.L.* ; Illig, T. ; Jarvik, G.P.* ; Johnson, J.A.* ; Kastelein, J.J.* ; Koenig, W.* ; LifeLines Cohort Study (*) ; Marz, W.* ; Mitchell, B.D.* ; Murray, S.S.* ; Oldehinkel, A.J.* ; Rader, D.J.* ; Reilly, M.P.* ; Reiner, A.P.* ; Schadt, E.E.* ; Silverstein, R.L.* ; Snieder, H.* ; Stanton, A.V.* ; Uitterlinden, A.G.* ; van der Harst, P.* ; van der Schouw, Y.T.* ; Samani, N.J.* ; Johnson, A.D.* ; Munroe, P.B.* ; de Bakker, P.I.* ; Zhu, X.* ; Levy, D.* ; Keating, B.J.* ; Asselbergs, F.W.*

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

Hum. Mol. Genet. 22, 1663-1678 (2013)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Genome-wide Association ; Histamine-receptor H-1 ; Coronary-heart-disease ; Pulse Pressure ; Expression ; P53 ; Hypertension ; Mdm2 ; Mice ; Metaanalysis
ISSN (print) / ISBN 0964-6906
e-ISSN 1460-2083
Journal Human Molecular Genetics
Quellenangaben Volume: 22, Issue: 8, Pages: 1663-1678 Article Number: , Supplement: ,
Publisher Oxford University Press
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology II (EPI2)
Institute of Genetic Epidemiology (IGE)
Research Unit Molecular Epidemiology (AME)