Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Jun;41(6):666-76.
doi: 10.1038/ng.361. Epub 2009 May 10.

Genome-wide association study identifies eight loci associated with blood pressure

Christopher Newton-Cheh  1 , Toby Johnson, Vesela Gateva, Martin D Tobin, Murielle Bochud, Lachlan Coin, Samer S Najjar, Jing Hua Zhao, Simon C Heath, Susana Eyheramendy, Konstantinos Papadakis, Benjamin F Voight, Laura J Scott, Feng Zhang, Martin Farrall, Toshiko Tanaka, Chris Wallace, John C Chambers, Kay-Tee Khaw, Peter Nilsson, Pim van der Harst, Silvia Polidoro, Diederick E Grobbee, N Charlotte Onland-Moret, Michiel L Bots, Louise V Wain, Katherine S Elliott, Alexander Teumer, Jian'an Luan, Gavin Lucas, Johanna Kuusisto, Paul R Burton, David Hadley, Wendy L McArdle; Wellcome Trust Case Control Consortium; Morris Brown, Anna Dominiczak, Stephen J Newhouse, Nilesh J Samani, John Webster, Eleftheria Zeggini, Jacques S Beckmann, Sven Bergmann, Noha Lim, Kijoung Song, Peter Vollenweider, Gerard Waeber, Dawn M Waterworth, Xin Yuan, Leif Groop, Marju Orho-Melander, Alessandra Allione, Alessandra Di Gregorio, Simonetta Guarrera, Salvatore Panico, Fulvio Ricceri, Valeria Romanazzi, Carlotta Sacerdote, Paolo Vineis, Inês Barroso, Manjinder S Sandhu, Robert N Luben, Gabriel J Crawford, Pekka Jousilahti, Markus Perola, Michael Boehnke, Lori L Bonnycastle, Francis S Collins, Anne U Jackson, Karen L Mohlke, Heather M Stringham, Timo T Valle, Cristen J Willer, Richard N Bergman, Mario A Morken, Angela Döring, Christian Gieger, Thomas Illig, Thomas Meitinger, Elin Org, Arne Pfeufer, H Erich Wichmann, Sekar Kathiresan, Jaume Marrugat, Christopher J O'Donnell, Stephen M Schwartz, David S Siscovick, Isaac Subirana, Nelson B Freimer, Anna-Liisa Hartikainen, Mark I McCarthy, Paul F O'Reilly, Leena Peltonen, Anneli Pouta, Paul E de Jong, Harold Snieder, Wiek H van Gilst, Robert Clarke, Anuj Goel, Anders Hamsten, John F Peden, Udo Seedorf, Ann-Christine Syvänen, Giovanni Tognoni, Edward G Lakatta, Serena Sanna, Paul Scheet, David Schlessinger, Angelo Scuteri, Marcus Dörr, Florian Ernst, Stephan B Felix, Georg Homuth, Roberto Lorbeer, Thorsten Reffelmann, Rainer Rettig, Uwe Völker, Pilar Galan, Ivo G Gut, Serge Hercberg, G Mark Lathrop, Diana Zelenika, Panos Deloukas, Nicole Soranzo, Frances M Williams, Guangju Zhai, Veikko Salomaa, Markku Laakso, Roberto Elosua, Nita G Forouhi, Henry Völzke, Cuno S Uiterwaal, Yvonne T van der Schouw, Mattijs E Numans, Giuseppe Matullo, Gerjan Navis, Göran Berglund, Sheila A Bingham, Jaspal S Kooner, John M Connell, Stefania Bandinelli, Luigi Ferrucci, Hugh Watkins, Tim D Spector, Jaakko Tuomilehto, David Altshuler, David P Strachan, Maris Laan, Pierre Meneton, Nicholas J Wareham, Manuela Uda, Marjo-Riitta Jarvelin, Vincent Mooser, Olle Melander, Ruth J F Loos, Paul Elliott, Gonçalo R Abecasis, Mark Caulfield, Patricia B Munroe
Collaborators, Affiliations

Genome-wide association study identifies eight loci associated with blood pressure

Christopher Newton-Cheh et al. Nat Genet. 2009 Jun.

Abstract

Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N ≤ 71,225 European ancestry, N ≤ 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10(-24)), CYP1A2 (P = 1 × 10(-23)), FGF5 (P = 1 × 10(-21)), SH2B3 (P = 3 × 10(-18)), MTHFR (P = 2 × 10(-13)), c10orf107 (P = 1 × 10(-9)), ZNF652 (P = 5 × 10(-9)) and PLCD3 (P = 1 × 10(-8)) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.

PubMed Disclaimer

Conflict of interest statement

COMPETING INTERESTS STATEMENT

The following authors declare the following potential conflicts of interest: N.L., V.M., K.S., D.M.W. and X.Y. are all full-time employees at GlaxoSmithKline. P. Vollenweider and G.W received financial support from GlaxoSmithKline to assemble the CoLaus study. No other authors reported conflicts of interest.

Figures

Figure 1
Figure 1
Regional association plots of eight blood pressure loci. For each locus, we show the region extending to within 500kb of a SNP with P < 10−4 on either side. Statistical significance of associated SNPs at each locus are illustrated on the - log10(P) scale as a function of chromosomal position (NCBI Build 35). The sentinel SNP at each locus is shown in red. The correlation of the sentinel SNP to other SNPs at the locus is shown on a scale from minimal (gray and blue), to maximal (red). The meta-analysis result for stage 1 is shown with a red square. The joint analysis result (combined P) for stage 1+2a+2b is shown with an arrow. Fine-scale recombination rate from Myers et al is plotted in aqua.
Figure 2
Figure 2
Relationship of genome-wide significant loci to SBP, DBP and hypertension. Shown are the effects of each variant on continuous SBP and DBP and on the odds ratio for dichotomous hypertension compared to normotension (see Methods). For comparability, SBP and DBP effects are shown on the standard deviation scale (SBP SD = 16.6 mm Hg, DBP SD = 10.9 mm Hg). Alleles are coded as shown in Table 2.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ezzati M, Lopez AD, Rodgers A, Vander Hoorn S, Murray CJ. Selected major risk factors and global and regional burden of disease. Lancet. 2002;360:1347–60. - PubMed
    1. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360:1903–1913. - PubMed
    1. The world health report 2002. Reducing risks, promoting healthy life. World Health Organization; 2002. - PubMed
    1. Whelton PK, et al. Primary prevention of hypertension: clinical and public health advisory from The National High Blood Pressure Education Program. Jama. 2002;288:1882–8. - PubMed
    1. Havlik RJ, et al. Blood pressure aggregation in families. Am J Epidemiol. 1979;110:304–12. - PubMed

Publication types

MeSH terms

Grants and funding

-