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Genetic analysis of over one million people identifies 535 novel loci for blood pressure
Εvangelos Εvangelou, Helen R. Warren, David Mosén-Ansorena, Borbála Mifsud, Raha Pazoki, He Gao, Georgios Ntritsos, Niki Dimou, Claudia P. Cabrera, İbrahim Karaman, Fu Liang Ng, Marina Evangelou, Katarzyna Witkowska, Evan Tzanis, Jacklyn N. Hellwege, Ayush Giri, Digna R. Velez Edwards, Yan V. Sun, Kelly Cho, J. Michael Gaziano, Peter W.F. Wilson, Philip S. Tsao, Csaba P. Kövesdy, Tõnu Esko, Reedik Mägi, Lili Milani, Peter Almgren, Thibaud Boutin, Stéphanie Debette, Jun Ding, Franco Giulianini, Anne Jackson, Ruifang Li‐Gao, Wei‐Yu Lin, Jian’an Luan, Massimo Mangino, Christopher Oldmeadow, Bram P. Prins, Yong Qian, Muralidharan Sargurupremraj, Nabi Shah, Praveen Surendran, Sébastien Thériault, Niek Verweij, Sara M. Willems, Jinghua Zhao, Philippe Amouyel, John Connell, Renée de Mutsert, Alex S. F. Doney, Martin Farrall, Cristina Menni, Andrew D. Morris, Raymond Noordam, Guillaume Paré, Neil R Poulter, Denis C. Shields, Alice Stanton, Simon Thom, Gonçalo Abecasis, Najaf Amin, Dan E. Arking, Kristin L. Ayers, Caterina Barbieri, Chiara Batini, Tineka Blake, Murielle Bochud, Michael Boehnke, Eric Boerwinkle, Dorret I. Boomsma, Erwin P. Böttinger, Peter S. Braund, Marco Brumat, Archie Campbell, Harry Campbell, Aravinda Chakravarti, John C. Chambers, Ganesh Chauhan, Marina Ciullo, Massimiliano Cocca, Francis S. Collins, Heather J. Cordell, Gail Davies, Martin H. de Borst, Eco J. C. de Geus, Ian J. Deary, Joris Deelen, Fabiola Del Greco M, Cumhur Yusuf Demirkale, Marcus Dörr, Georg Ehret, Roberto Elosúa, Stefan Enroth, A. Mesut Erzurumluoglu, Teresa Ferreira, Mattias Frånberg, Oscar H. Franco, Ilaria Gandin, Paolo Gasparini, Vilmantas Giedraitis, Christian Gieger, Giorgia Girotto, Anuj Goel, Alan J. Gow, Vilmundur Guðnason, Xiuqing Guo, Ulf Gyllensten, Anders Hamsten, Tamara B. Harris, Sarah E. Harris, Catharina A. Hartman, Aki S. Havulinna, Andrew A. Hicks, Edith Hofer, Albert Hofman, Jouke‐Jan Hottenga, Jennifer E. Huffman, Shih‐Jen Hwang, Erik Ingelsson, Alan James, Rick Jansen, Marjo‐Riitta Järvelin, Roby Joehanes, Åsa Johansson, Andrew D. Johnson, Peter K. Joshi, J. Wouter Jukema, Antti Jula, Mika Kähönen, Sekar Kathiresan, Bernard Keavney, Kay‐Tee Khaw, Paul Knekt, Jo Knight, Ivana Kolčić, Jaspal S. Kooner, Seppo Koskinen, Kati Kristiansson, Zoltán Kutalik, Maris Laan, Marty Larson, Lenore J. Launer, Benjamin C Lehne, Terho Lehtimäki, Daniel Levy, David C. Liewald, Li Lin, Lars Lind, Cecilia M. Lindgren, Ching‐Ti Liu, Ruth J. F. Loos, Lorna M. Lopez, Lingchan Lu, Leo‐Pekka Lyytikäinen, Anubha Mahajan, Chrysovalanto Mamasoula, Jaume Marrugat, Jonathan Marten, Yuri Milaneschi, Anna Morgan, Andrew P. Morris, Alanna C. Morrison, Peter J. Munson, Mike A. Nalls, Priyanka Nandakumar, Christopher P. Nelson, Christopher Newton‐Cheh, Teemu Niiranen, Ilja M. Nolte, Teresa Nutile, Albertine J. Oldehinkel, Ben A. Oostra, Paul F. O’Reilly, Elin Org, Sandosh Padmanabhan, Walter Palmas, Arno Palotie, Alison Pattie, Brenda W.J.H. Penninx, Markus Perola, Annette Peters, Ozren Polašek, Peter P. Pramstaller, Nguyen Quang Tri, Olli T. Raitakari, Meixia Ren, Rainer Rettig, Kenneth Rice, Paul M. Ridker, J. REID, Harriëtte Riese, Samuli Ripatti, Antonietta Robino, Lynda M. Rose, Jerome I. Rotter, Igor Rudan, Daniella Ruggiero, Yasaman Saba, Cinzia Sala, Veikko Salomaa, Nilesh J. Samani, Antti‐Pekka Sarin, Rheinhold Schmidt, Helena Schmidt, Nick Shrine, David S. Siscovick, Albert V. Smith, Harold J. Schneider, Siim Sõber, Rossella Sorice, John M. Starr, David J. Stott, David P. Strachan, Rona J. Strawbridge, Johan Sundström, Morris A. Swertz, Kent D. Taylor, Alexander Teumer, Martin D. Tobin, Daniela Toniolo, Michela Traglia, Stella Trompet, Jaakko Tuomilehto, Christophe Tzourio, André G. Uitterlinden, Ahmad Vaez, Peter J. van der Most, Cornelia M. van Duijn, Anne‐Claire Vergnaud, Germaine C. Verwoert, Véronique Vitart, Uwe Völker, Péter Vollenweider, Dragana Vuckovic, Hugh Watkins, Sarah H. Wild, Gonneke Willemsen, James F. Wilson, Alan F. Wright, Jie Yao, Tatijana Zemunik, Weihua Zhang, John Attia, Adam S. Butterworth, D. I. Chasman, David Conen, Francesco Cucca, John Danesh, Caroline Hayward, Joanna M. M. Howson, Markku Laakso, Edward G. Lakatta, Claudia Langenberg, Ollie Melander, Dennis O. Mook‐Kanamori, Patricia B. Munroe, Lorenz Risch, Robert A. Scott, Rodney J. Scott, Peter Sever, Tim D. Spector, Pim van der Harst, Nicholas J. Wareham, Eleftheria Zeggini, Morris J. Brown, Andres Metspalu, Adriana M. Hung, Christopher J. O’Donnell, Todd L. Edwards, Bruce M. Psaty, Ioanna Tzoulaki, Michael R. Barnes, Louise V. Wain, Paul Elliott, Mark J. Caulfield
Bibliographic record
VenuebioRxiv (Cold Spring Harbor Laboratory) · 2017
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsMcMaster UniversityInstitut universitaire de cardiologie et de pneumologie de Québec
FundersNational Heart, Lung, and Blood InstituteNational Institute of Diabetes and Digestive and Kidney DiseasesBarts and The London School of Medicine and DentistryMedical Research CouncilCanadian Institutes of Health ResearchHorizon 2020 Framework ProgrammeNational Institutes of HealthUK Dementia Research InstituteChina Scholarship CouncilPublic Health EnglandZonMwNational Medical Research CouncilKing's College LondonWellcome TrustCancer Research UKImperial College Healthcare NHS TrustNetherlands Heart InstituteGlaxoSmithKlineImperial College LondonNovo Nordisk FondenCisco SystemsAgence Nationale de la RechercheMinistero della SaluteAlzheimer's SocietyBritish Heart FoundationBrigham and Women's HospitalUniversité LavalNovo NordiskNational Institute on AgingNational Institute for Health and Care ResearchBritish Lung FoundationNational Institute for Health Research Health Protection Research UnitEU Joint Programme – Neurodegenerative Disease ResearchU.S. Department of Veterans Affairs
KeywordsBlood pressurePulse pressureDiseaseMedicineBiologyInternal medicine
Abstract
Abstract High blood pressure is the foremost heritable global risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits to date (systolic, diastolic, pulse pressure) in over one million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also reveal shared loci influencing lifestyle exposures. Our findings offer the potential for a precision medicine strategy for future cardiovascular disease prevention.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.003
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.004
Threshold uncertainty score0.013
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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 head0.016
GPT teacher head0.248
Teacher spread0.232 · how far apart the two teachers sit on this one work
Validation status
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), 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
Citations13
Published2017
Admission routes2
Has abstractyes