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Record W2557046497 · doi:10.1038/ncomms13357

A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

2016· article· en· W2557046497 on OpenAlexaff
Janina S. Ried, Janina Jeff M., Audrey Y. Chu, Jennifer L. Bragg‐Gresham, Jenny van Dongen, Jennifer E. Huffman, Tarunveer S. Ahluwalia, Gemma Cadby, Niina Eklund, Joel Eriksson, Tõnu Esko, Mary F. Feitosa, Anuj Goel, Mathias Gorski, Caroline Hayward, Nancy L. Heard‐Costa, Anne Jackson, Eero Jokinen, Stavroula Kanoni, Kati Kristiansson, Zoltán Kutalik, Jari Lahti, Jian’an Luan, Reedik Mägi, Anubha Mahajan, Massimo Mangino, Carolina Medina‐Gómez, Keri L. Monda, Ilja M. Nolte, Louis Përusse, Inga Prokopenko, Lu Qi, Lynda M. Rose, Erika Salvi, Megan Therese Smith, Harold Snieder, Alena Stančáková, Ioanna Tachmazidou, Alexander Teumer, Guðmar Þorleifsson, Pim van der Harst, Ryan W. Walker, Sophie R. Wang, Sarah H. Wild, Sara M. Willems, Andrew Wong, Weihua Zhang, Eva Albrecht, Alexessander Couto Alves, Stephan J. L. Bakker, Cristina Barlassina, Traci M. Bartz, John Beilby, Claire Bellis, Richard N. Bergman, Sven Bergmann, John Blangero, Matthias Blüher, Eric Boerwinkle, Lori L. Bonnycastle, Stefan R. Bornstein, Marcel Bruinenberg, Harry Campbell, Yii-Der Ida Chen, Charleston W. K. Chiang, Peter S. Chines, Francis S. Collins, Francesco Cucca, L. Adrienne Cupples, Francesca D’Avila, Eco J. C. de Geus, George Dedoussis, Maria Dimitriou, Angela Döring, Johan G. Eriksson, Aliki‐Eleni Farmaki, Martin Farrall, Teresa Ferreira, Krista Fischer, Nita G. Forouhi, Nele Friedrich, Anette P. Gjesing, Nicola Glorioso, Mariaelisa Graff, Harald Grallert, Niels Grarup, Jürgen Gräßler, Jagvir Grewal, Anders Hamsten, Marie Neergaard Harder, Catharina A. Hartman, Maija Hassinen, Nicholas D. Hastie, Andrew T. Hattersley, Aki S. Havulinna, Markku Heliövaara, Hans L. Hillege, Albert Hofman, Oddgeir L. Holmen, Georg Homuth, Jouke‐Jan Hottenga, Jennie Hui, Lise Lotte N. Husemoen, Pirro G. Hysi, Aaron Isaacs, Till Ittermann, Shapour Jalilzadeh, Torben Jørgensen, Antti Jula, Johanne Marie Justesen, Anne E. Justice, Mika Kähönen, Maria Karaleftheri, Kay‐Tee Khaw, Sirkka Keinänen‐Kiukaanniemi, Leena Kinnunen, Paul Knekt, Heikki A. Koistinen, Ivana Kolčić, Ishminder K. Kooner, Seppo Koskinen, Péter Kovács, Theodosios Kyriakou, Tomi Laitinen, Claudia Langenberg, Alex Lewin, Peter Lichtner, Cecilia M. Lindgren, Jaana Lindström, Allan Linneberg, Roberto Lorbeer, Mattias Lorentzon, Robert Luben, Valeriya Lyssenko, Satu Männistö, Paolo Manunta, Irene Mateo Leach, Wendy L. McArdle, Barbara McKnight, Karen L. Mohlke, Evelin Mihailov, Lili Milani, Rebecca Mills, May E. Montasser, Andrew P. Morris, Gabriele Müller, Arthur W. Musk, Narisu Narisu, Ken K. Ong, Ben A. Oostra, Clive Osmond, Aarno Palotie, James S. Pankow, Lavinia Paternoster, Brenda W.J.H. Penninx, Irene Pichler, Maria Grazia Pilia, Ozren Polašek, Peter P. Pramstaller, Olli T. Raitakari, Tuomo Rankinen, D. C. Rao, Nigel W. Rayner, Rasmus Ribel‐Madsen, Treva Rice, Marcus Richards, Paul M. Ridker, Fernando Rivadeneira, Serena Sanna, Mark A. Sarzynski, Salome Scholtens, Robert A. Scott, Sylvain Sebért, Lorraine Southam, Thomas Sparsø, Valgerður Steinthórsdóttir, Kathleen Stirrups, Ronald P. Stolk, Konstantin Strauch, Heather M. Stringham, Morris A. Swertz, Amy J. Swift, Anke Tönjes, Emmanouil Tsafantakis, Peter J. van der Most, Jana V. van Vliet‐Ostaptchouk, Liesbeth Vandenput, Erkki Vartiainen, Cristina Venturini, Niek Verweij, Jorma Viikari, Véronique Vitart, Marie‐Claude Vohl, Judith M. Vonk, Gérard Waeber, Elisabeth Widén, Gonneke Willemsen, Tom Wilsgaard, Thomas W. Winkler, Alan F. Wright, Laura M. Yerges-Armstrong, Wei Zhao, M. Carola Zillikens, Dorret I. Boomsma, Claude Bouchard, John C. Chambers, Daniel I. Chasman, Daniele Cusi, Ron T. Gansevoort, Christian Gieger, Torben Hansen, Andrew A. Hicks, Frank B. Hu, Kristian Hveem, Marjo‐Riitta Järvelin, Eero Kajantie, Jaspal S. Kooner, Diana Kuh, Johanna Kuusisto, Markku Laakso, Timo A. Lakka, Terho Lehtimäki, Andres Metspalu, Inger Njølstad, Claes Ohlsson, Albertine J. Oldehinkel, Lyle J. Palmer, Oluf Pedersen, Markus Perola, Annette Peters, Bruce M. Psaty, Hannu Puolijoki, Rainer Rauramaa, Igor Rudan, Veikko Salomaa, Peter Schwarz, Alan R. Shudiner, Jan Smit, Thorkild I. A. Sørensen, Timothy D. Spector, Kāri Stefánsson, Michael Stümvoll, Angelo Tremblay, Jaakko Tuomilehto, André G. Uitterlinden, Matti Uusitupa, Uwe Völker, Péter Vollenweider, Nicholas J. Wareham, Hugh Watkins, James F. Wilson, Eleftheria Zeggini, Gonçalo R. Abecasis, Michael Boehnke, Ingrid B. Borecki, Panos Deloukas, Cornelia M. van Duijn, Caroline S. Fox, Leif Groop, Iris M. Heid, David J. Hunter, Robert C. Kaplan, Mark I. McCarthy, Kari E. North, Jeffrey R. O’Connell, David Schlessinger, Unnur Þorsteinsdóttir, David P. Strachan, Timothy M. Frayling, Joel N. Hirschhorn, Martina Müller‐Nurasyid, Ruth J. F. Loos

Bibliographic record

VenueNature Communications · 2016
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic and phenotypic traits in livestock
Canadian institutionsCentre for Global Health ResearchUniversité Laval
FundersEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Center for Advancing Translational SciencesNational Institute of Diabetes and Digestive and Kidney DiseasesNational Heart, Lung, and Blood InstituteNovo Nordisk FondenNational Institute for Health and Care ResearchNational Cancer InstituteLundbeckfondenWellcome TrustMedical Research CouncilMcKnight Foundation
KeywordsPrincipal component analysisAnthropometryMeta-analysisComponent (thermodynamics)BiologyGeneticsBody shapeComputational biologyComputer scienceEvolutionary biologyMedicineArtificial intelligenceInternal medicinePhysics

Abstract

fetched live from OpenAlex

Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.

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 imitation

Not 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)0.013
metaresearch head score (Gemma)0.022
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Meta-analysis · Consensus signal: Meta-analysis
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.013
Threshold uncertainty score0.070

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0130.022
Meta-epidemiology (narrow)0.0030.001
Meta-epidemiology (broad)0.0040.023
Bibliometrics0.0040.006
Science and technology studies0.0010.001
Scholarly communication0.0030.001
Open science0.0010.002
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0030.000

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 head0.064
GPT teacher head0.334
Teacher spread0.270 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designMeta-analysis
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".

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Citations92
Published2016
Admission routes1
Has abstractyes

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Same venueNature CommunicationsSame topicGenetic and phenotypic traits in livestockFrench-language works237,207