Genome-wide association study of blood pressure and hypertension
Open accessAbstract
Blood pressure is a major cardiovascular disease risk factor. To date, few variants associated with interindividual blood pressure variation have been identified and replicated. Here we report results of a genome-wide association study of systolic (SBP) and diastolic (DBP) blood pressure and hypertension in the CHARGE Consortium (n = 29,136), identifying 13 SNPs for SBP, 20 for DBP and 10 for hypertension at P < 4 × 10−7. The top ten loci for SBP and DBP were incorporated into a risk score; mean BP and prevalence of hypertension increased in relation to the number of risk alleles carried. When ten CHARGE SNPs for each trait were included in a joint meta-analysis with the Global BPgen Consortium (n = 34,433), four CHARGE loci attained genome-wide significance (P < 5 × 10−8) for SBP (ATP2B1, CYP17A1, PLEKHA7, SH2B3), six for DBP (ATP2B1, CACNB2, CSK-ULK3, SH2B3, TBX3-TBX5, ULK4) and one for hypertension (ATP2B1). Identifying genes associated with blood pressure advances our understanding of blood pressure regulation and highlights potential drug targets for the prevention or treatment of hypertension.
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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 [275]
The Results (page unavailable) identify CYP17A1 as genome-wide significant for systolic blood pressure, but list only ATP2B1 as genome-wide significant for hypertension. The Discussion (page unavailable) also describes CYP17A1 as associated with a rare Mendelian form of hypertension. Thus this GWAS supports a blood-pressure association, but not the claim that it identified CYP17A1 through a significant association with hypertension itself. (LLM, conf=0.87)
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- Authors
- Levy, D., Ehret, G. B., Rice, K., Verwoert, G. C., Launer, L. J., Dehghan, A., Glazer, N. L., Morrison, A. C., Johnson, A. D., Aspelund, T., Aulchenko, Y., Lumley, T., Köttgen, A., Vasan, R. S., Rivadeneira, F., Eiriksdottir, G., Guo, X., Arking, D. E., Mitchell, G. F., Mattace-Raso, F. U. S., Smith, A. V., Taylor, K., Scharpf, R. B., Hwang, S.-J., Sijbrands, E. J. G., Bis, J., Harris, T. B., Ganesh, S. K., O'Donnell, C. J., Hofman, A., Rotter, J. I., Coresh, J., Benjamin, E. J., Uitterlinden, A. G., Heiss, G., Fox, C. S., Witteman, J. C. M., Boerwinkle, E., Wang, T. J., Gudnason, V., Larson, M. G., Chakravarti, A., Psaty, B. M., & van Duijn, C. M.
- Affiliations
- Framingham Heart Study (US)
- Johns Hopkins University (US)
- University of Washington (US)
- Erasmus MC (NL)
- National Institutes of Health (US)
- The University of Texas Health Science Center at Houston (US)
- National Heart, Lung, and Blood Institute (US)
- University of Iceland (IS)
- Boston University (US)
- Cedars-Sinai Medical Center (US)
- Icelandic Heart Association (IS)
- Harvard University (US)
- Group Health Cooperative (US)
- Corresponding author
- Levy, Daniel
- ORCID
- Levy, Daniel
- Ehret, Georg B
- Rice, Kenneth
- Launer, Lenore J
- Dehghan, Abbas
- Glazer, Nicole L
- Morrison, Alanna C
- Johnson, Andrew D
- Aspelund, Thor
- Aulchenko, Yurii
- Köttgen, Anna
- Vasan, Ramachandran S
- Rivadeneira, Fernando
- Guo, Xiuqing
- Arking, Dan E
- Mitchell, Gary F
- Mattace-Raso, Francesco U S
- Smith, Albert V
- Taylor, Kent
- Scharpf, Robert B
- Hwang, Shih-Jen
- Sijbrands, Eric J G
- Bis, Joshua
- Harris, Tamara B
- Ganesh, Santhi K
- Rotter, Jerome I
- Coresh, Josef
- Benjamin, Emelia J
- Uitterlinden, André G
- Heiss, Gerardo
- Fox, Caroline S
- Boerwinkle, Eric
- Wang, Thomas J
- Gudnason, Vilmundur
- Larson, Martin G
- Chakravarti, Aravinda
- Psaty, Bruce M
- Venue
- Nature Genetics
- Published
- 2009-05-10
- Volume
- 41
- Issue
- 6
- Pages
- 677-687
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC2998712
- OpenAlex
- W2001629081
- Semantic Scholar
- 6fdc08f8708718ee3edc03d2ab8cec5a60dabb3a
- Cited by
- 1,364
- References
- 49
- Citations by year
- 2026: 25 · 2025: 25 · 2024: 37 · 2023: 47 · 2022: 45 · 2021: 62 · 2020: 46 · 2019: 59 · 2018: 85 · 2017: 104 · 2016: 109 · 2015: 88 · 2014: 104 · 2013: 109 · 2012: 141
- Type
- dissertation
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (911-03-012, 175.010.200)
- National Institutes of Health (n01hc085082-026, n01hc085081-021, n01hc045133-001, n01ag12100-57-0-2, n01hc085079-024, n01hc015103-009, n01hc085084-005, n01hc55021-47-0-1, n01hc085085-011, n01hc085083-027, n01hc55020-39-0-0, n01hc085080-026, n01hc55016-37-0-0, n01hc055022-024, n01hc085086-022, n01hc55019-35-0-1, n01hc55018-38-0-1, n01hc25195-41-0-1, n01hc55222-0-0-0, n02hl64278-6-0-0, n01hc075150-004, n01hc035129-010, n01hc55015-48-0-1)
- U.S. Public Health Service (HHSN 268200625226C)
- National Institute on Aging (N01-AG012100)
- National Heart, Lung, and Blood Institute (N01-HC-85081, N01HC85085, N01-HC55022, N01 HC085086, N01HC-85083, N01 HC055016, N01-HC-55018, N01 HC 55020, N01 HC085079, N01‐HC25195, N01 HC 55019, N01HC85082, N01HC‐75150, N01 HC85086, R01 HL-59367, R01HL087652, N01 HC055020, N01 HC035129, N02 HL064278, N01HC85080, N02- HL-64278, N01 HC055018, N01 HC015103, N01 HC55222, N01-HC-025195, U10HL054512, N01-HC55016, R01HL087641, N01 HC055022, R01HL059367, U01HL080295, N01 HC055019, N01 HC055222, N01‐HC‐55015, N01-HC55021, N01 HC075150, N01 HC055021, R37HL051021, N01 HC055015, N01 HC045133, R01HL086694, N01-HC85079, N01-HC85084)
- National Human Genome Research Institute (U01HG004402)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK063491)
- National Center for Research Resources (UL1RR025005)
- 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, CHARGE consortium, risk score, ATP2B1, CYP17A1, PLEKHA7, SH2B3, CACNB2, ULK4, blood pressure regulation, therapeutic target
- MeSH terms
- Blood Pressure, Cell Line, Chromosome Mapping, Chromosomes, Human, Diastole, Gene Expression Regulation, Humans, Hypertension, Liver, Lymphocytes, Phenotype, Systole, Meta-Analysis as Topic, Prevalence, Odds Ratio, Risk Assessment, Genome-Wide Association Study, Genetic Association Studies
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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