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Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney
Louise V. Wain, Ahmad Vaez, Rick Jansen, Roby Joehanes, Peter J. van der Most, A. Mesut Erzurumluoglu, Paul F. O’Reilly, Claudia P. Cabrera, Helen R. Warren, Lynda M. Rose, Germaine C. Verwoert, Jouke‐Jan Hottenga, Rona J. Strawbridge, Tõnu Esko, Dan E. Arking, Shih-Jen Hwang, Xiuqing Guo, Zoltán Kutalik, Stella Trompet, Nick Shrine, Alexander Teumer, Janina S. Ried, Joshua C. Bis, Albert V. Smith, Najaf Amin, Ilja M. Nolte, Leo‐Pekka Lyytikäinen, Anubha Mahajan, Nicholas J. Wareham, Edith Hofer, Peter K. Joshi, Kati Kristiansson, Michela Traglia, Aki S. Havulinna, Anuj Goel, Mike A. Nalls, Siim Sõber, Dragana Vuckovic, Jian’an Luan, Fabiola Del Greco M, Kristin L. Ayers, Jaume Marrugat, Daniela Ruggiero, Lorna M. Lopez, Teemu Niiranen, Stefan Enroth, Anne Jackson, Christopher P. Nelson, Jennifer E. Huffman, Weihua Zhang, Jonathan Marten, Ilaria Gandin, Sarah E. Harris, Tatijana Zemunik, Yingchang Lu, Εvangelos Εvangelou, Nabi Shah, Martin H. de Borst, Massimo Mangino, Bram P. Prins, Archie Campbell, Ruifang Li‐Gao, Ganesh Chauhan, Christopher Oldmeadow, Gonçalo Abecasis, Maryam Abedi, Caterina Barbieri, Michael R. Barnes, Chiara Batini, John Beilby, Tineka Blake, Michael Boehnke, Erwin P. Böttinger, Peter S. Braund, Morris J. Brown, Marco Brumat, Harry Campbell, John C. Chambers, Massimiliano Cocca, Francis S. Collins, John Connell, Heather J. Cordell, Jeffrey Damman, Gail Davies, Eco J. C. de Geus, Renée de Mutsert, Joris Deelen, Yusuf Demirkale, Alex S. F. Doney, Marcus Dörr, Martin Farrall, Teresa Ferreira, Mattias Frånberg, He Gao, Vilmantas Giedraitis, Christian Gieger, Franco Giulianini, Alan J. Gow, Anders Hamsten, Tamara B. Harris, Albert Hofman, Jennie Hui, Marjo‐Riitta Järvelin, Åsa Johansson, Andrew D. Johnson, Antti Jula, Mika Kähönen, Sekar Kathiresan, Kay‐Tee Khaw, Ivana Kolčić, Seppo Koskinen, Claudia Langenberg, Marty Larson, Lenore J. Launer, Benjamin Lehne, David C. Liewald, Li Lin, Lars Lind, François Mach, Chrysovalanto Mamasoula, Cristina Menni, Borbála Mifsud, Yuri Milaneschi, Anna Morgan, Andrew D. Morris, Alanna C. Morrison, Peter J. Munson, Priyanka Nandakumar, Quang Tri Nguyen, Teresa Nutile, Albertine J. Oldehinkel, Ben A. Oostra, Elin Org, Sandosh Padmanabhan, Aarno Palotie, Guillaume Paré, Alison Pattie, Brenda W.J.H. Penninx, Neil R Poulter, Peter P. Pramstaller, Olli T. Raitakari, Meixia Ren, Kenneth Rice, Paul M. Ridker, Harriëtte Riese, Samuli Ripatti, Antonietta Robino, Jerome I. Rotter, Igor Rudan, Yasaman Saba, Aude Saint Pierre, Cinzia Sala, Antti-Pekka Sarin, Reinhold Schmidt, Rodney J. Scott, Marc A. Seelen, Denis C. Shields, David S. Siscovick, Rossella Sorice, Alice Stanton, David J. Stott, Johan Sundström, Morris A. Swertz, Kent D. Taylor, Simon Thom, Ioanna Tzoulaki, Christophe Tzourio, André G. Uitterlinden, Uwe Völker, Péter Vollenweider, Gonneke Willemsen, Alan F. Wright, Jie Yao, Sébastien Thériault, David Conen, John Attia, Peter Sever, Stéphanie Debette, Dennis O. Mook‐Kanamori, Eleftheria Zeggini, Tim D. Spector, Pim van der Harst, Anne‐Claire Vergnaud, Ruth J. F. Loos, Ozren Polašek, John M. Starr, Giorgia Girotto, Caroline Hayward, Jaspal S. Kooner, Cecilia M. Lindgren, Véronique Vitart, Nilesh J. Samani, Jaakko Tuomilehto, Ulf Gyllensten, Paul Knekt, Ian J. Deary, Marina Ciullo, Roberto Elosúa, Bernard Keavney, Andrew A. Hicks, Robert A. Scott, Paolo Gasparini, Maris Laan, Ching‐Ti Liu, Hugh Watkins, Catharina A. Hartman, Veikko Salomaa, Daniela Toniolo, Markus Perola, James F. Wilson, Helena Schmidt, Wei Zhao, Terho Lehtimäki, Cornelia M. van Duijn, Vilmundur Guðnason, Bruce M. Psaty, Annette Peters, Rainer Rettig, J. Wouter Jukema, David P. Strachan, Walter Palmas, Andres Metspalu, Erik Ingelsson, Dorret I. Boomsma, Oscar H. Franco, Murielle Bochud, Christopher Newton‐Cheh, Patricia B. Munroe, Paul Elliott, Daniel I. Chasman, Aravinda Chakravarti, Jo Knight, Andrew P. Morris, Daniel Levy, Martin D. Tobin, Harold Snieder, Mark J. Caulfield, Georg Ehret
Bibliographic record
VenueHypertension · 2017
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsPopulation Health Research InstituteMcMaster University
FundersNational Center for Research ResourcesNational Institute of Child Health and Human DevelopmentNational Institute of Allergy and Infectious DiseasesNational Cancer InstituteNational Human Genome Research InstituteNational Institute of Mental HealthUppsala Multidisciplinary Center for Advanced Computational ScienceMünchner Zentrum für GesundheitswissenschaftenAgència de Gestió d'Ajuts Universitaris i de RecercaErasmus Universitair Medisch Centrum RotterdamCambridge Institute for Medical Research, University of CambridgeEconomic and Social Research CouncilBiotechnology and Biological Sciences Research CouncilDirectorate for Biological SciencesNational Institutes of HealthCentre for Cognitive Ageing and Cognitive EpidemiologyMutuelle Générale de l'Education NationaleCentro de Investigación Biomédica en Red Enfermedades CardiovascularesAcademy of FinlandServierKarl-Franzens-Universität GrazPaavo Nurmen SäätiöSigrid Juséliuksen SäätiöUniversité de BordeauxUniversitair Medisch Centrum GroningenSydäntutkimussäätiöProvincia autonoma di Bolzano - Alto AdigeSchweizerische HerzstiftungNational Institute for Health Research Health Protection Research UnitVetenskapsrådetFondation de FranceSigne ja Ane Gyllenbergin SäätiöReuter FoundationJuho Vainion SäätiöNederlandse Organisatie voor Wetenschappelijk OnderzoekTurun Yliopistollinen KeskussairaalaSuomen KulttuurirahastoDiabetes FondsErasmus Medisch CentrumDiabetesliittoSanofiLeids Universitair Medisch CentrumNierstichtingSvenska Sällskapet för Medicinsk ForskningFondation pour la Recherche MédicaleAmgenFondazione CariploYrjö Jahnssonin SäätiöKelaNational Institute of General Medical SciencesOrionin TutkimussäätiöEesti TeadusagentuurAge UKHrvatska Zaklada za ZnanostRussian Foundation for Basic ResearchNational Eye InstitutePublic Health EnglandFoundation for Cardiovascular ResearchZonMwNational Heart, Lung, and Blood InstituteUniversiteit LeidenSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungNational Science FoundationFondation LeducqNational Institute on AgingUniversität GreifswaldMedical Research CouncilHjärt-LungfondenUniversity of DundeeJohns Hopkins UniversityHome OfficeWellcome TrustAgence Nationale de la RechercheWetenschappelijk Onderzoek- en DocumentatiecentrumUniversity of EdinburghUniversität BaselNational Center for Advancing Translational SciencesBundesministerium für Bildung und ForschungEuropean Science FoundationTerveyden ja hyvinvoinnin laitosImperial College LondonKing's College LondonGeneralitat de CatalunyaEuropean CommissionKnut och Alice Wallenbergs StiftelseNIHR Cambridge Biomedical Research CentreScottish Funding CouncilHôpitaux Universitaires de GenèveChina Scholarship CouncilBritish Heart FoundationAustrian Science FundNational Institute for Health and Care ResearchAstraZenecaMinistry of Cultural AffairsMedizinische Universität GrazEmil Aaltosen SäätiöCompagnia di San PaoloMRC-PHE Centre for Environment and HealthBristol-Myers SquibbHelsingin YliopistoVrije Universiteit AmsterdamUnderstanding SocietyScottish GovernmentImperial College Healthcare NHS TrustCancer Research UKUniversity of EssexJuvenile Diabetes Research Foundation InternationalChief Scientist Office, Scottish Government Health and Social Care DirectorateMinistero della SaluteInstitut National de la Santé et de la Recherche MédicaleUniversitätsspital BaselWake Forest UniversityDevelopment of Innovative Strategies for a Transdisciplinary approach to ALZheimer's diseaseTampereen TuberkuloosisäätiöRijksuniversiteit GroningenUniversity of LeicesterNational Institute of Diabetes and Digestive and Kidney DiseasesRoyal SocietyFoundation for the National Institutes of HealthPfizer
KeywordsBlood pressureGenome-wide association studyLocus (genetics)GeneBiologyGeneticsComputational biologyGenetic associationBioinformaticsMedicineEndocrinologyGenotypeSingle-nucleotide polymorphism
Abstract
Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project–based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7 , TNXB , LRP12 , LOC283335 , SEPT9 , and AKT2 , and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA . Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.
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 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)0.002
metaresearch head score (Gemma)0.004
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 score0.005
Threshold uncertainty score0.011
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.003 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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 head0.035
GPT teacher head0.266
Teacher spread0.230 · 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
Citations169
Published2017
Admission routes1
Has abstractyes