Genome-wide association study identifies eight loci associated with blood pressure
Open accessAbstract
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 2.5m 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 8 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.
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Two genome-wide association studies have identified the CYP17A1 locus as a gene associated with hypertension.
“Two genome-wide association studies have identified the CYP17A1 locus as a gene associated with hypertension (274,275).”
From The Molecular Biology, Biochemistry, and Physiology of Human Steroidogenesis and Its Disorders (2011) · cites this paper as [274]
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Genetic Variation and Neuroimaging Measures in Alzheimer Disease
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Inherited Disorders of Renal Salt Homeostasis
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- Authors
- Wellcome Trust Case Control Consortium, Newton-Cheh, C., Johnson, T., Gateva, V., Tobin, M. D., Bochud, M., Coin, L., Najjar, S. S., Zhao, J. H., Heath, S. C., Eyheramendy, S., Papadakis, K., Voight, B. F., Scott, L. J., Zhang, F., Farrall, M., Tanaka, T., Wallace, C., Chambers, J. C., Khaw, K.-T., Nilsson, P., van der Harst, P., Polidoro, S., Grobbee, D. E., Onland-Moret, N. C., Bots, M. L., Wain, L. V., Elliott, K. S., Teumer, A., Luan, J., Lucas, G., Kuusisto, J., Burton, P. R., Hadley, D., McArdle, W. L., Brown, M., Dominiczak, A., Newhouse, S. J., Samani, N. J., Webster, J., Zeggini, E., Beckmann, J. S., Bergmann, S., Lim, N., Song, K., Vollenweider, P., Waeber, G., Waterworth, D. M., Yuan, X., Groop, L., Orho-Melander, M., Allione, A., Di Gregorio, A., Guarrera, S., Panico, S., Ricceri, F., Romanazzi, V., Sacerdote, C., Vineis, P., Barroso, I., Sandhu, M. S., Luben, R. N., Crawford, G. J., Jousilahti, P., Perola, M., Boehnke, M., Bonnycastle, L. L., Collins, F. S., Jackson, A. U., Mohlke, K. L., Stringham, H. M., Valle, T. T., Willer, C. J., Bergman, R. N., Morken, M. A., Döring, A., Gieger, C., Illig, T., Meitinger, T., Org, E., Pfeufer, A., Wichmann, H. E., Kathiresan, S., Marrugat, J., O'Donnell, C. J., Schwartz, S. M., Siscovick, D. S., Subirana, I., Freimer, N. B., Hartikainen, A.-L., McCarthy, M. I., O'Reilly, P. F., Peltonen, L., Pouta, A., de Jong, P. E., Snieder, H., van Gilst, W. H., Clarke, R., Goel, A., Hamsten, A., Peden, J. F., Seedorf, U., Syvänen, A.-C., Tognoni, G., Lakatta, E. G., Sanna, S., Scheet, P., Schlessinger, D., Scuteri, A., Dörr, M., Ernst, F., Felix, S. B., Homuth, G., Lorbeer, R., Reffelmann, T., Rettig, R., Völker, U., Galan, P., Gut, I. G., Hercberg, S., Lathrop, G. M., Zelenika, D., Deloukas, P., Soranzo, N., Williams, F. M., Zhai, G., Salomaa, V., Laakso, M., Elosua, R., Forouhi, N. G., Völzke, H., Uiterwaal, C. S., van der Schouw, Y. T., Numans, M. E., Matullo, G., Navis, G., Berglund, G., Bingham, S. A., Kooner, J. S., Connell, J. M., Bandinelli, S., Ferrucci, L., Watkins, H., Spector, T. D., Tuomilehto, J., Altshuler, D., Strachan, D. P., Laan, M., Meneton, P., Wareham, N. J., Uda, M., Jarvelin, M.-R., Mooser, V., Melander, O., Loos, R. J., Elliott, P., Abecasis, G. R., Caulfield, M., & Munroe, P. B.
- Affiliations
- SIB Swiss Institute of Bioinformatics (CH)
- University of Michigan (US)
- University of Leicester (GB)
- Centre Hospitalier Universitaire Vaudois (CH)
- Imperial College London (GB)
- National Institutes of Health (US)
- University of Cambridge (GB)
- Pontificia Universidad Católica de Chile (CL)
- St George's, University of London (GB)
- Broad Institute (US)
- King's College London (GB)
- Centre for Human Genetics (GB)
- Memorial Hospital of South Bend (US)
- Queen Mary University of London (GB)
- Lund University (SE)
- Institute for Scientific Interchange (IT)
- University Medical Center Utrecht (NL)
- Universität Greifswald (DE)
- Addenbrooke's Hospital (GB)
- University of Eastern Finland (FI)
- University of Bristol (GB)
- University of Glasgow (GB)
- Aberdeen Royal Infirmary (GB)
- GlaxoSmithKline (United Kingdom) (GB)
- Federico II University Hospital (IT)
- Piedmont Reference Center for Epidemiology and Cancer Prevention (IT)
- Finnish Institute for Health and Welfare (FI)
- University of Helsinki (FI)
- University of North Carolina at Chapel Hill (US)
- University of Southern California (US)
- Helmholtz Munich (DE)
- University of Tartu (EE)
- University of Washington (US)
- Centro de Investigación Biomédica en Red (ES)
- University of California, Los Angeles (US)
- University of Oulu (FI)
- University Medical Center Groningen (NL)
- University of Oxford (GB)
- Karolinska University Hospital (SE)
- University of Münster (DE)
- Uppsala University (SE)
- Mario Negri Institute for Pharmacological Research (IT)
- National Academies of Sciences, Engineering, and Medicine (US)
- The University of Texas MD Anderson Cancer Center (US)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- Inserm (FR)
- Azienda Sanitaria di Firenze (IT)
- Corresponding author
- Abecasis, Gonçalo R
- Caulfield, Mark
- Munroe, Patricia B
- ORCID
- Johnson, Toby
- Tobin, Martin D
- Bochud, Murielle
- Coin, Lachlan
- Najjar, Samer S
- Zhao, Jing Hua
- Heath, Simon C
- Eyheramendy, Susana
- Voight, Benjamin F
- Scott, Laura J
- Zhang, Feng
- Farrall, Martin
- Tanaka, Toshiko
- Wallace, Chris
- Chambers, John C
- Khaw, Kay-Tee
- Nilsson, Peter
- Polidoro, Silvia
- Grobbee, Diederick E
- Bots, Michiel L
- Wain, Louise V
- Elliott, Katherine S
- Teumer, Alexander
- Luan, Jian'an
- Lucas, Gavin
- Kuusisto, Johanna
- Brown, Morris
- Dominiczak, Anna
- Newhouse, Stephen J
- Samani, Nilesh J
- Zeggini, Eleftheria
- Beckmann, Jacques S
- Bergmann, Sven
- Lim, Noha
- Waterworth, Dawn M
- Yuan, Xin
- Groop, Leif
- Allione, Alessandra
- Guarrera, Simonetta
- Panico, Salvatore
- Ricceri, Fulvio
- Romanazzi, Valeria
- Sacerdote, Carlotta
- Vineis, Paolo
- Barroso, Inês
- Sandhu, Manjinder S
- Luben, Robert N
- Perola, Markus
- Boehnke, Michael
- Bonnycastle, Lori L
- Collins, Francis S
- Mohlke, Karen L
- Stringham, Heather M
- Willer, Cristen J
- Bergman, Richard N
- Gieger, Christian
- Meitinger, Thomas
- Org, Elin
- Wichmann, H Erich
- Kathiresan, Sekar
- Marrugat, Jaume
- Siscovick, David S
- McCarthy, Mark I
- Peltonen, Leena
- Snieder, Harold
- Clarke, Robert
- Goel, Anuj
- Hamsten, Anders
- Seedorf, Udo
- Lakatta, Edward G
- Sanna, Serena
- Scheet, Paul
- Schlessinger, David
- Scuteri, Angelo
- Dörr, Marcus
- Ernst, Florian
- Felix, Stephan B
- Homuth, Georg
- Völker, Uwe
- Galan, Pilar
- Gut, Ivo G
- Deloukas, Panos
- Soranzo, Nicole
- Williams, Frances M
- Zhai, Guangju
- Salomaa, Veikko
- Laakso, Markku
- Forouhi, Nita G
- Völzke, Henry
- Uiterwaal, Cuno S
- Numans, Mattijs E
- Matullo, Giuseppe
- Kooner, Jaspal S
- Bandinelli, Stefania
- Ferrucci, Luigi
- Watkins, Hugh
- Spector, Tim D
- Tuomilehto, Jaakko
- Altshuler, David
- Strachan, David P
- Laan, Maris
- Meneton, Pierre
- Wareham, Nicholas J
- Uda, Manuela
- Mooser, Vincent
- Melander, Olle
- Loos, Ruth JF
- Elliott, Paul
- Abecasis, Gonçalo R
- Caulfield, Mark
- Munroe, Patricia B
- Venue
- Nature Genetics
- Published
- 2009-05-10
- Volume
- 41
- Issue
- 6
- Pages
- 666-676
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC2891673
- OpenAlex
- W2129254992
- Semantic Scholar
- d077e8342784a92ad47913f20325b86c93e521ff
- Cited by
- 1,215
- References
- 85
- Citations by year
- 2026: 18 · 2025: 17 · 2024: 15 · 2023: 32 · 2022: 33 · 2021: 35 · 2020: 40 · 2019: 50 · 2018: 65 · 2017: 77 · 2016: 83 · 2015: 78 · 2014: 92 · 2013: 111 · 2012: 137
- FWCI
- 90.93
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- St George's Online Research Archive (St George's University of London) (acceptedVersion)
- PubMed Central (acceptedVersion)
- SERVAL (Université de Lausanne) (acceptedVersion, other-oa)
- IRIS (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- UNICA IRIS Institutional Research Information System (University of Cagliari) (submittedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- Leicester Research Archive (University of Leicester) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- mediaTUM (Technical University of Munich) (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Explore Bristol Research (submittedVersion)
- Bristol Research (University of Bristol) (submittedVersion)
- ResearchSpace (University of Auckland) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- National Science Foundation (310030)
- American Diabetes Association
- AstraZeneca
- GlaxoSmithKline
- Massachusetts General Hospital
- Compagnia di San Paolo
- Foundation for Cardiovascular Research
- Donovan Family Foundation
- Wellcome Trust (068545/Z/02), G0000934, 061858, 077011, 088885, 077016, WT088885/Z/09/Z, 079557, 068545, 077016/Z/05/Z, 079895, 090532, 076113/B/04/Z, 089061, 076113, 070191/z/03/z)
- King's College Hospital NHS Foundation Trust
- Institute for Scientific Interchange
- Cancer Research UK (10589)
- National Institute for Health and Care Research
- British Heart Foundation (LSHM-CT-2007-037273, PG/02/128, FS/05/061/19501, SP/04/002)
- King's College London
- European Commission (01ZZ0103, LSHM-CT-2007–037273, 201413, 01ZZ0403, 03ZIK012, QLG1‐CT‐2000‐01643, AEP/90/05, 01ZZ9603, 821336)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (116323, 112552, 122661, 111361, 111362, 3100AO-116323/1, 118065, 201413, 129494, 124243, 310030)
- Bundesministerium für Bildung und Forschung (01EZ0874, 03ZIK012, 01ZZ0403, 01ZZ0103, 01ZZ9603)
- Nierstichting
- Ministero della Salute
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (916.76.170, 19501)
- Lunds Universitet
- Universitair Medisch Centrum Utrecht
- Knut och Alice Wallenbergs Stiftelse
- Stockholms Läns Landsting (562183)
- Vetenskapsrådet
- Sydäntutkimussäätiö
- Malmö Högskola
- Oulun Yliopisto
- Université de Lausanne
- Institut National de la Recherche Agronomique
- Region Skåne
- Conservatoire National des Arts et Métiers
- National Institutes of Health (G0000934, 5k23hl083102-02, NO1-AG-1–2109, 6r01hl087679-03, 5rl1mh083268-05, 6u54rr020278-06, 068545/Z/02, 079895, RL1MH083268, DK062370)
- U.S. Public Health Service (263-MA-410953)
- Medical Research Council (MC_qA137934, 068545/Z/02, G0000934, G9521010D, G0501942)
- Agència de Gestió d'Ajuts Universitaris i de Recerca
- Instituto de Salud Carlos III (RD 06/0009)
- NIHR Cambridge Biomedical Research Centre
- National Institute on Aging (N01AG-821336, N01-AG-12109, NO1-AG-1-2109, 821336, N01[AG]916413, 263MD821336)
- National Heart, Lung, and Blood Institute (K23-HL-083102, R01HL087676, K23 HL80025, K23HL080025, R01HL056931, R01 HL087679)
- National Institute of Mental Health (RL1-MH083268)
- National Institute on Drug Abuse (U54DA021519)
- National Human Genome Research Institute (Z01HG000024)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-072193, R01DK072193, U01DK062370, R56DK062370, U01DK062418, DK-062370, R01DK062370)
- National Institute of Environmental Health Sciences (P30ES007033)
- National Center for Research Resources (U54-RR020278)
- National Institute on Minority Health and Health Disparities (263-MD-916413, 263MD 821336)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (N01-HD-1-3107)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- blood pressure, hypertension, systolic blood pressure, diastolic blood pressure, genetic loci, single nucleotide polymorphisms, CYP17A1, CYP1A2, FGF5, SH2B3, MTHFR, cardiovascular disease, European ancestry
- MeSH terms
- Blood Pressure, Cardiovascular Diseases, Chromosome Mapping, Diastole, DNA-Binding Proteins, Europe, Humans, India, Proteins, Steroid 17-alpha-Hydroxylase, Systole, Genetic Variation, Open Reading Frames, Cytochrome P-450 CYP1A2, Polymorphism, Single Nucleotide, Methylenetetrahydrofolate Reductase (NADPH2), White People, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, Fibroblast Growth Factor 5, Phospholipase C delta, Genome-Wide Association Study
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