Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk
Open accessAbstract
Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.
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In a genetic risk score analysis combining lead variants at all seven LTL-associated loci in 22,233 CAD cases and 64,762 controls, alleles associated with shorter LTL were associated with increased risk of CAD (21% (95% CI: 5-35%) per standard deviation in LTL, p=0.014).
“Moreover, a genetic risk score analysis combining lead variants at all seven loci in 22,233 coronary artery disease cases and 64,762 controls showed an association of the alleles associated with shorter LTL with increased risk of CAD (21% (95% CI: 5–35%) per standard deviation in LTL, p=0.014).”
From Identification of seven loci affecting mean telomere length and their association with disease (2013) · cites this paper as [31]
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Inherited Disorders of Renal Salt Homeostasis
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- Authors
- The International Consortium for Blood Pressure Genome-Wide Association Studies
- Venue
- Nature
- Published
- 2011-09-11
- Volume
- 478
- Issue
- 7367
- Pages
- 103-109
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3340926
- OpenAlex
- W2101605059
- Cited by
- 2,033
- References
- 31
- Citations by year
- 2026: 45 · 2025: 52 · 2024: 81 · 2023: 74 · 2022: 90 · 2021: 111 · 2020: 123 · 2019: 138 · 2018: 192 · 2017: 197 · 2016: 191 · 2015: 197 · 2014: 175 · 2013: 198 · 2012: 147
- FWCI
- 107.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, other-oa)
- Discovery Research Portal (University of Dundee) (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- PubMed Central (acceptedVersion)
- St George's Online Research Archive (St George's University of London) (acceptedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- SERVAL (Université de Lausanne) (acceptedVersion, other-oa)
- IRIS (submittedVersion)
- Lirias (submittedVersion, other-oa)
- Apollo (University of Cambridge) (submittedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Civil War Book Review (submittedVersion)
- FedUni ResearchOnline (Federation University Australia) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- HAL (submittedVersion)
- Americanae (AECID Library) (submittedVersion, other-oa)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- University of Regensburg Publication Server (University of Regensburg) (submittedVersion)
- UnissResearch (Università degli Studi di Sassari) (submittedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- Leicester Research Archive (University of Leicester) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Site cant be reached (submittedVersion)
- RWTH Publications (RWTH Aachen) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Queen Mary Research Online (Queen Mary University of London) (submittedVersion)
- Bristol Research (University of Bristol) (submittedVersion)
- National University of Singapore (submittedVersion)
- Open Research (University of Surrey) (submittedVersion)
- Hirsla (Landspítali University Hospital) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion)
- Apollo
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Howard Hughes Medical Institute (#55005617)
- Wellcome Trust (068545/Z/02), 080747/Z/06/Z, 079895/Z/06/Z, 077016/Z/05/Z, 079895, 090532, 079895/Z/06/B, 070191/z/03/z)
- National Institute for Health and Care Research (NF-SI-0507-10315)
- British Heart Foundation (RG/08/013/25942, SP/08/005/25115, PG97027, RG/08/008/25291, PG/02/128, G0501942, FS05/125, RG/07/005/23633, RG08/01, CH/03/001, PG/97012, RG/98002, SP/04/002, RG/07/008/23674, RG/08/014/24067)
- Kidney Research UK (RP24/2/2006)
- Agence Nationale de la Recherche (ANR-10-INBS-0001)
- National Institutes of Health (n01hc95164-17-0-1, 5r01ag032098-05, n01hc085082-026, n01hc085081-021, n01ag062101-007, n01hc045133-001, n01ag12100-57-0-2, n01hc085079-024, n01hc015103-009, n01hc085084-005, n01hc55021-47-0-1, n01ag062103-006, n01hc085085-011, n01hc085083-027, n01hc95165-34-0-1, n01hc55020-39-0-0, n01hc085080-026, n01hc55016-37-0-0, n01hc055022-024, n01hc95161-24-0-1, n01hc095169-003, 5u01hg004423-02, 5k12rr023250-05, n01hc95166-21-0-1, n01hc085086-022, 5r01hl087700-03, n01hc95162-31-0-1, n01hc55019-35-0-1, n01hc95168-27-0-1, n01hc95160-18-0-1, 6r01hl087679-03, n01hc095167-000, n01hc55018-38-0-1, 5rl1mh083268-05, n01hc25195-41-0-1, n01hc95163-22-0-1, 5p20rr020649-03, 6u54rr020278-06, n01hc55222-0-0-0, 5r01hl043851-10, n01hc95159-40-0-1, n01hc075150-004, n01hc035129-010, 10,11, 5u01ns069208-04, n01hc55015-48-0-1)
- Agency for Healthcare Research and Quality (HS06516)
- Canadian Institutes of Health Research (MOP--82810, #MOP77682, MOP172605)
- Biotechnology and Biological Sciences Research Council (G20234)
- Japan Society for the Promotion of Science (21390099, 20390185)
- National Institute on Aging (R01-AG-18728, N01‐AG‐6–2101, N01-AG-12109, N01-AG12100, N01AG6210, R01AG018728, AG 13196, 1R01AG032098-01A, N01-AG-62103, R01AG017644)
- National Heart, Lung, and Blood Institute (N01-HC-85081, HL45508, N01HC85085, R01HL071205, N01-HC55022, N01HC-85083, N01 HC-95159, N01-HC-95160, N01-HC-55018, R01HL073410, HL043851, N01 HC-95168, R01HL071252, 5R01 HL087679-02, 5R01HL08770002, N01HC15103, HL085144, R01HL085251, U01HL084729, N01 HC95167, N01 HC 55020, (N01-HC-95163, R01HL086718, N01‐HC25195, R01HL060919, R01HL071259, N01 HC 55019, N01HC85082, N01HC‐75150, N01 HC85086, R01 HL-59367, N01 HC-95161, N01 HC95165, R01HL088120, N01HC95164, R01HL087652, R01HL071251, U01HL084756, N01HC85080, R01HL087660, N02- HL-64278, U01HL054466, U01HL054471, R01HL098283, N01 HC55222, R01HL087647, HL087647, HL-53353, HL-084729, K23HL080025, R01HL071051, N01‐HC‐45133, R01HL056931, R01HL071250, U10HL054512, N01-HC55016, R01HL087641, HL 080025, R01HL059367, R01HL060894, R01HL061019, R01HL105756, R01HL053353, U01HL080295, HL36310, U01HL072515, R01HL088119, N01‐HC‐95166, R01HL06094, R01HL085144, R01HL071258, HL54512, U01HL054473, HL098283, N01‐HC‐55015, N01 HC-95162, N01-HC55021, R37HL051021, R01HL036310, HL086718, R01HL089650, R01HL086694, N01-HC85079, HL-87660, N01-HC85084, N01HC35129, N01 HC95169)
- National Institute of Mental Health (R01MH063706, 1RL1MH083268-01, 5R01 MH63706:02)
- National Human Genome Research Institute (U01HG004735, U01-HG004423, U01HG004726, HG005581, U01HG004422, U01HG004738, U01HG004399, R01HG003054, U01HG004402, U01HG004728, U01HG004415, U01HG004446, U01HG004729, U01HG004438, U01HG004436, RC2HG005581, HHSN268200782096C, HG 003054)
- National Cancer Institute (R01CA094143, P01CA087969, U01CA086308, P01CA055075)
- National Institute of General Medical Sciences (S06 GM008016-380111, S06GM008016, S06 GM008016-320107, U01GM074518)
- Fogarty International Center (R01TW008288, TW05596, TW008288, R03TW007165, R01TW005596)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK063491, DK075787, DK-072193, R01DK078150, R01DK072193, DK078150, R01DK058845, R01DK066574, DK56350, U01DK062418, DK-062370, R01DK075787, P30DK063491, P30DK056350)
- National Institute of Neurological Disorders and Stroke (R01NS42733, R01NS039987, U01-NS069208, R01 NS-39987, R01NS042733)
- National Institute of Environmental Health Sciences (ES 10126, P30ES010126, P30ES007033)
- National Institute of Dental and Craniofacial Research (U01DE01899, U01DE018903)
- National Center for Research Resources (U54-RR020278, K12-RR023250, UL1RR025005, RR20649, RR024156, M01RR016500, M01RR010284, M01RR000425, M01RR 16500, M01-RR00425)
- National Center for Advancing Translational Sciences
- National Institute on Minority Health and Health Disparities (263MD9164, 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, cardiovascular risk, stroke, coronary artery disease, left ventricular wall thickness, genetic loci, polygenic risk score, GUCY1A3, NPR3, ADM, furin, GNAS, genetic variants, renal function
- MeSH terms
- Africa, Asia, Blood Pressure, Cardiovascular Diseases, Coronary Artery Disease, Europe, Humans, Hypertension, Kidney Diseases, Genetic Predisposition to Disease, Stroke, Polymorphism, Single Nucleotide, Genome-Wide Association Study
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.
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