Title: Blood Pressure Loci Identified with a Gene-Centric Array
Authors: Johnson, Toby ×
Gaunt, Tom R
Newhouse, Stephen J
Padmanabhan, Sandosh
Tomaszewski, Maciej
Kumari, Meena
Morris, Richard W
Tzoulaki, Ioanna
O'Brien, Eoin T
Poulter, Neil R
Sever, Peter
Shields, Denis C
Thom, Simon
Wannamethee, Sasiwarang G
Whincup, Peter H
Brown, Morris J
Connell, John M
Dobson, Richard J
Howard, Philip J
Mein, Charles A
Onipinla, Abiodun
Shaw-Hawkins, Sue
Zhang, Yun
Smith, George Davey
Day, Ian N. M
Lawlor, Debbie A
Goodall, Alison H
Fowkes, F. Gerald
Abecasis, Goncalo R
Elliott, Paul
Gateva, Vesela
Braund, Peter S
Burton, Paul R
Nelson, Christopher P
Tobin, Martin D
van der Harst, Pim
Glorioso, Nicola
Neuvrith, Hani
Salvi, Erika
Staessen, Jan A
Stucchi, Andrea
Devos, Nabila
Jeunemaitre, Xavier
Plouin, Pierre-Francois
Tichet, Jean
Juhanson, Peeter
Org, Elin
Putku, Margus
Sober, Siim
Veldre, Gudrun
Viigimaa, Margus
Levinsson, Anna
Rosengren, Annika
Thelle, Dag S
Hastie, Claire E
Hedner, Thomas
Lee, Wai K
Melander, Olle
Wahlstrand, Bjoern
Hardy, Rebecca
Wong, Andrew
Cooper, Jackie A
Palmen, Jutta
Chen, Limin
Stewart, Alexandre F. R
Wells, George A
Westra, Harm-Jan
Wolfs, Marcel G. M
Clarke, Robert
Franzosi, Maria Grazia
Goel, Anuj
Hamsten, Anders
Lathrop, Mark
Peden, John F
Seedorf, Udo
Watkins, Hugh
Ouwehand, Willem H
Sambrook, Jennifer
Stephens, Jonathan
Casas, Juan-Pablo
Drenos, Fotios
Holmes, Michael V
Kivimaki, Mika
Shah, Sonia
Shah, Tina
Talmud, Philippa J
Whittaker, John
Wallace, Chris
Delles, Christian
Laan, Mans
Kuh, Diana
Humphries, Steve E
Nyberg, Fredrik
Cusi, Daniele
Roberts, Robert
Newton-Cheh, Christopher
Franke, Lude
Stanton, Alice V
Dominiczak, Anna F
Farrall, Martin
Hingorani, Aroon D
Samani, Nilesh J
Caulfield, Mark J
Munroe, Patricia B #
Issue Date: Dec-2011
Publisher: American Society of Human Genetics
Series Title: American Journal of Human Genetics vol:89 issue:6 pages:688-700
Abstract: Raised blood pressure (BP) is a major risk factor for cardiovascular disease. Previous studies have identified 47 distinct genetic variants robustly associated with BP, but collectively these explain only a few percent of the heritability for BP phenotypes. To find additional BP loci, we used a bespoke gene-centric array to genotype an independent discovery sample of 25,118 individuals that combined hypertensive case-control and general population samples. We followed up four SNPs associated with BP at our p < 8.56 x 10(-7) study-specific significance threshold and six suggestively associated SNPs in a further 59,349 individuals. We identified and replicated a SNP at LSP1/TNNT3, a SNP at MTHFR-NPPB independent (r(2) = 0.33) of previous reports, and replicated SNPs at AGT and ATP2B1 reported previously. An analysis of combined discovery, and follow-up data identified SNPs significantly associated with BP at p < 8.56 x 10(-7) at four further loci (NPR3, FIFE, NOS3, and SOX6). The high number of discoveries made with modest genotyping effort can be attributed to using a large-scale yet targeted genotyping array and to the development of a weighting scheme that maximized power when meta-analyzing results from samples ascertained with extreme phenotypes, in combination with results from nonascertained or population samples. Chromatin immunoprecipitation and transcript expression data highlight potential gene regulatory mechanisms at the MTHFR and NOS3 loci. These results provide candidates for further study to help dissect mechanisms affecting BP and highlight the utility of studying SNPs and samples that are independent of those studied previously even when the sample size is smaller than that in previous studies.
ISSN: 0002-9297
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Hypertension and Cardiovascular Epidemiology
× corresponding author
# (joint) last author

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