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Record W4396531762 · doi:10.1038/s41588-024-01714-w

Genome-wide analysis in over 1 million individuals of European ancestry yields improved polygenic risk scores for blood pressure traits

2024· article· en· W4396531762 on OpenAlexaff
Jacob M. Keaton, Zoha Kamali, Tian Xie, Ahmad Vaez, Ariel Williams, Slavina B. Goleva, Alireza Ani, Εvangelos Εvangelou, Jacklyn N. Hellwege, Loic Yengo, William J. Young, Matthew Traylor, Ayush Giri, Zhili Zheng, Jian Zeng, Daniel I. Chasman, Andrew P. Morris, Mark J. Caulfield, Shih-Jen Hwang, Jaspal S. Kooner, David Conen, John Attia, Alanna C. Morrison, Ruth J. F. Loos, Kati Kristiansson, Reinhold Schmidt, Andrew A. Hicks, Peter P. Pramstaller, Christopher P. Nelson, Nilesh J. Samani, Lorenz Risch, Ulf Gyllensten, Olle Melander, Harriëtte Riese, James F. Wilson, Harry Campbell, Stephen S. Rich, Bruce M. Psaty, Yingchang Lu, Jerome I. Rotter, Xiuqing Guo, Kenneth Rice, Péter Vollenweider, Johan Sundström, Claudia Langenberg, Martin D. Tobin, Vilmantas Giedraitis, Jian’an Luan, Jaakko Tuomilehto, Zoltán Kutalik, Samuli Ripatti, Veikko Salomaa, Giorgia Girotto, Stella Trompet, J. Wouter Jukema, Pim van der Harst, Paul M. Ridker, Franco Giulianini, Véronique Vitart, Anuj Goel, Hugh Watkins, Sarah E. Harris, Ian J. Deary, Peter J. van der Most, Albertine J. Oldehinkel, Bernard Keavney, Caroline Hayward, Archie Campbell, Michael Boehnke, Laura J. Scott, Thibaud Boutin, Chrysovalanto Mamasoula, Marjo‐Riitta Järvelin, Annette Peters, Christian Gieger, Edward G. Lakatta, Francesco Cucca, Jennie Hui, Paul Knekt, Stefan Enroth, Martin H. de Borst, Ozren Polašek, Maria Pina Concas, Eulalia Catamo, Massimiliano Cocca, Ruifang Li-Gao, Edith Hofer, Helena Schmidt, Beatrice Spedicati, David P. Strachan, Maris Laan, Alexander Teumer, Marcus Dörr, Vilmundur Guðnason, James P. Cook, Daniela Ruggiero, Ivana Kolčić, Eric Boerwinkle, Michela Traglia, Terho Lehtimäki, Olli Raitakari, Andrew D. Johnson, Christopher Newton‐Cheh, Morris J. Brown, Anna F. Dominiczak, Peter J. Sever, Neil Poulter, John C. Chambers, Roberto Elosúa, David Siscovick, Tõnu Esko, Andres Metspalu, Rona J. Strawbridge, Markku Laakso, Anders Hamsten, Jouke‐Jan Hottenga, Eco J. C. de Geus, Andrew D. Morris, Ilja M. Nolte, Yuri Milaneschi, Jonathan Marten, Alan F. Wright, Eleftheria Zeggini, Joanna M. M. Howson, Christopher J. O’Donnell, Tim D. Spector, Mike A. Nalls, Eleanor M. Simonsick, Ching‐Ti Liu, Cornelia M. van Duijn, John N. Danesh, Cristina Menni, Nicholas J. Wareham, Kay-Tee Khaw, Yan V. Sun, Peter W.F. Wilson, Kelly Cho, Peter M. Visscher, Joshua C. Denny, Daniel Levy, Patricia B. Munroe, William J. Young, Todd L. Edwards, Harold Snieder

Bibliographic record

VenueNature Genetics · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsCentre for Global Health ResearchMcMaster UniversityPopulation Health Research Institute
FundersNational Institute of Diabetes and Digestive and Kidney DiseasesNational Heart, Lung, and Blood InstituteNational Institute on AgingMedical Research CouncilSchool of Medicine, Duke UniversityNational Institutes of HealthIsfahan University of Medical SciencesBrigham and Women's HospitalBritish Heart FoundationEesti TeadusagentuurNovo Nordisk FondenIsrael Science FoundationUniversity of OxfordKing's College LondonDepartment of Health and Social CareU.S. Department of Veterans AffairsNational Institute of Neurological Disorders and StrokeNational Institute for Health and Care Research
KeywordsBiologyPolygenic risk scoreMultifactorial InheritanceGenome-wide association studyQuantitative trait locusGeneticsBlood pressureGenomeEvolutionary biologyGeneSingle-nucleotide polymorphismGenotype

Abstract

fetched live from OpenAlex

Abstract Hypertension affects more than one billion people worldwide. Here we identify 113 novel loci, reporting a total of 2,103 independent genetic signals ( P < 5 × 10 −8 ) from the largest single-stage blood pressure (BP) genome-wide association study to date ( n = 1,028,980 European individuals). These associations explain more than 60% of single nucleotide polymorphism-based BP heritability. Comparing top versus bottom deciles of polygenic risk scores (PRSs) reveals clinically meaningful differences in BP (16.9 mmHg systolic BP, 95% CI, 15.5–18.2 mmHg, P = 2.22 × 10 −126 ) and more than a sevenfold higher odds of hypertension risk (odds ratio, 7.33; 95% CI, 5.54–9.70; P = 4.13 × 10 −44 ) in an independent dataset. Adding PRS into hypertension-prediction models increased the area under the receiver operating characteristic curve (AUROC) from 0.791 (95% CI, 0.781–0.801) to 0.826 (95% CI, 0.817–0.836, ∆AUROC, 0.035, P = 1.98 × 10 −34 ). We compare the 2,103 loci results in non-European ancestries and show significant PRS associations in a large African-American sample. Secondary analyses implicate 500 genes previously unreported for BP. Our study highlights the role of increasingly large genomic studies for precision health research.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.078
Threshold uncertainty score0.784

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.009
GPT teacher head0.268
Teacher spread0.259 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations182
Published2024
Admission routes1
Has abstractyes

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