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Record W2519445944 · doi:10.1038/ng.3667

The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

2016· review· en· W2519445944 on OpenAlexaff
Georg Ehret, Teresa Ferreira, Daniel I. Chasman, Anne Jackson, Ellen M. Schmidt, Toby Johnson, Guðmar Þorleifsson, Jian’an Luan, Stavroula Kanoni, Ann-Kristin Petersen, Vasyl Pihur, Rona J. Strawbridge, Dmitry Shungin, Maria Hughes, Osorio Meirelles, Marika Kaakinen, Nabila Bouatia‐Naji, Kati Kristiansson, Sonia Shah, Marcus E. Kleber, Xiuqing Guo, Leo‐Pekka Lyytikäinen, Niclas Eriksson, Ilja M. Nolte, Patrik K. E. Magnusson, Elias Salfati, Lοukianos S. Rallidis, Elizabeth Theusch, Andrew J. Smith, Lasse Folkersen, Kate Witkowska, Tune H. Pers, Roby Joehanes, Stuart K. Kim, Lazaros Lataniotis, Rick Jansen, Andrew D. Johnson, Helen R. Warren, Young Jin Kim, Wei Zhao, Ying Wu, Bamidele O. Tayo, Murielle Bochud, Devin Absher, Linda S. Adair, Najaf Amin, Dan E. Arking, Tomas Axelsson, Damiano Baldassarre, Beverley Balkau, Stefania Bandinelli, Michael R. Barnes, Inês Barroso, Steve Bevan, Gyða Björnsdóttir, Michael Boehnke, Eric Boerwinkle, Lori L. Bonnycastle, Dorret I. Boomsma, Stefan R. Bornstein, Morris J. Brown, Michel Burnier, Claudia Cabrera, John C. Chambers, I‐Shou Chang, Ching‐Yu Cheng, Peter S. Chines, Ren-Hua Chung, Francis S. Collins, John Connell, Angela Döring, Jean Dallongeville, John Danesh, Ulf dé Fairé, Graciela Delgado, Anna F. Dominiczak, Alex S. F. Doney, Fotios Drenos, Sarah Edkins, John D. Eicher, Roberto Elosúa, Stefan Enroth, Jeanette Erdmann, Per Eriksson, Tõnu Esko, Εvangelos Εvangelou, Alun Evans, Tove Fall, Martin Farrall, Janine F. Felix, Jean Ferrières, Luigi Ferrucci, Myriam Fornage, Terrence Forrester, Nora Franceschini, Oscar H Franco Duran, Anders Franco‐Cereceda, Ross M. Fraser, Santhi K. Ganesh, He Gao, Karl Gertow, Francesco Gianfagna, Bruna Gigante, Franco Giulianini, Anuj Goel, Alison H. Goodall, Mark O Goodarzi, Mathias Gorski, Jürgen Gräßler, Christopher J. Groves, Vilmundur Guðnason, Ulf Gyllensten, Göran Hallmans, Anna-Liisa Hartikainen, Maija Hassinen, Aki S. Havulinna, Caroline Hayward, Serge Herçberg, Karl-Heinz Herzig, Andrew A. Hicks, Aroon D. Hingorani, Joel N. Hirschhorn, Albert Hofman, Jostein Holmen, Oddgeir L. Holmen, Jouke‐Jan Hottenga, Phil Howard, Chao A. Hsiung, Steven C. Hunt, M. Arfan Ikram, Thomas Illig, Carlos Iribarren, Richard A. Jensen, Mika Kähönen, Hyun Min Kang, Sekar Kathiresan, Brendan J. Keating, Kay‐Tee Khaw, Yun Kyoung Kim, Eric H. Kim, Mika Kivimäki, Norman Klopp, Genovefa Kolovou, Pirjo Komulainen, Jaspal S. Kooner, Gülüm Kosova, Ronald M. Krauss, Diana Kuh, Zoltán Kutalik, Johanna Kuusisto, Kirsti Kvaløy, Timo A. Lakka, Sang Lee, I‐Te Lee, Wen‐Jane Lee, Daniel Levy, Kae-Woei Liang, Honghuang Lin, Lin Li, Jaana Lindström, Stéphane Lobbens, Satu Männistö, Gabriele Müller, Martina Müller‐Nurasyid, François Mach, Hugh S. Markus, Eirini Marouli, Mark I. McCarthy, Colin A. McKenzie, Pierre Meneton, Cristina Menni, Andres Metspalu, Vladan Mijatovic, Leena Moilanen, May E. Montasser, Andrew D Morris, Alanna C. Morrison, Antonella Mulas, Ramaiah Nagaraja, Narisu Narisu, Kjell Nikus, Christopher J. O’Donnell, Paul F. O’Reilly, Ken K. Ong, Fred Paccaud, Cameron D. Palmer, Afshin Parsa, Nancy L. Pedersen, Brenda W.J.H. Penninx, Markus Perola, Annette Peters, Neil Poulter, Peter P. Pramstaller, Bruce M. Psaty, Thomas Quertermous, Dabeeru C Rao, Asif Rasheed, N. William Rayner, Frida Renström, Rainer Rettig, Kenneth Rice, Robert Roberts, Lynda M. Rose, Jacques Rossouw, Nilesh J. Samani, Serena Sanna, Jouko Saramies, Heribert Schunkert, Sylvain Sebért, Wayne H-H Sheu, Young-Ah Shin, Xueling Sim, Johannes H. Smit, Albert V. Smith, Maria X. Sosa, Tim D. Spector, Alena Stančáková, Alice Stanton, Kathleen Stirrups, Heather M. Stringham, Johan Sundström, Amy J. Swift, Ann‐Christine Syvänen, E Shyong Tai, Toshiko Tanaka, Kirill V. Tarasov, Alexander Teumer, Unnur Thorsteinsdottir, Martin D. Tobin, Elena Tremoli, André G. Uitterlinden, Matti Uusitupa, Ahmad Vaez, Dhananjay Vaidya, Cornelia M. van Duijn, Erik P.A. van Iperen, Ramachandran S. Vasan, Germaine C. Verwoert, Jarmo Virtamo, Véronique Vitart, Benjamin F. Voight, Péter Vollenweider, Aline Wagner, Louise V. Wain, Nicholas J. Wareham, Hugh Watkins, Alan B. Weder, Harm-Jan Westra, Rainford Wilks, Tom Wilsgaard, James F Wilson, Tien Yin Wong, Tsun-Po Yang, Jie Yao, Loïc Yengo, Weihua Zhang, Jing Hua Zhao, Xiaofeng Zhu, Pascal Bovet, Karen L Mohlke, Danish Saleheen, Jong‐Young Lee, Paul Elliott, Hinco J. Gierman, Cristen J. Willer, Lude Franke, G. Kees Hovingh, Kent D. Taylor, George Dedoussis, Peter S. Sever, Andrew Wong, Lars Lind, Themistocles L. Assimes, Inger Njølstad, Peter E. H. Schwarz, Claudia Langenberg, Harold Snieder, Mark J. Caulfield, Olle Melander, Markku Laakso, Juha Saltevo, Rainer Rauramaa, Jaakko Tuomilehto, Erik Ingelsson, Terho Lehtimäki, Kristian Hveem, Walter Palmas, Winfried März, Meena Kumari, Veikko Salomaa, Yii‐Der I. Chen, Jerome I. Rotter, Philippe Froguel, Marjo‐Riitta Järvelin, Edward G. Lakatta, Kari Kuulasmaa, Paul W. Franks, Anders Hamsten, H-Erich Wichmann, Kāri Stefánsson, Paul M. Ridker, Ruth J. F. Loos, Aravinda Chakravarti, Panos Deloukas, Andrew P. Morris, Christopher Newton‐Cheh, Patricia B. Munroe

Bibliographic record

VenueNature Genetics · 2016
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsCanadian Heart Research Centre
FundersEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Center for Research ResourcesNational Institute of Diabetes and Digestive and Kidney DiseasesNational Center for Advancing Translational SciencesWellcome TrustNational Human Genome Research InstituteNational Eye InstituteNational Institute on AgingFogarty International CenterNational Heart, Lung, and Blood InstituteNational Institute of Mental HealthMedical Research CouncilVersus ArthritisNational Institute of Neurological Disorders and StrokeNational Institute of General Medical SciencesNational Institute for Health and Care ResearchNational Institutes of HealthNational Institute of Environmental Health SciencesLundbeckfondenNational Cancer InstituteBritish Heart Foundation
KeywordsBiologySingle-nucleotide polymorphismGenome-wide association studyBlood pressureSNPGenetic associationGenotypeGeneticsGenetic architectureInternal medicineBioinformaticsQuantitative trait locusEndocrinologyGeneMedicine

Abstract

fetched live from OpenAlex

To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.

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)0.002
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Research integrity
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.939
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0020.000
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 head0.023
GPT teacher head0.331
Teacher spread0.308 · 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.

Study designNot applicable
Domainnot available
GenreReview

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

Citations438
Published2016
Admission routes1
Has abstractyes

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