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Record W4294904260 · doi:10.1038/s41588-022-01165-1

Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention

2022· review· en· W4294904260 on OpenAlexafffund
Zhe Wang, Andrew Emmerich, Nicolas J. Pillon, Timothy M. Moore, Daiane Hemerich, Marilyn C. Cornelis, Eugenia Mazzaferro, Siacia Broos, Tarunveer S. Ahluwalia, Traci M. Bartz, Amy R. Bentley, Lawrence F. Bielak, Audrey Y. Chu, Diane J. Berry, Rajkumar Dorajoo, Nicole Dueker, Elisa Kasbohm, Bjarke Feenstra, Mary F. Feitosa, Christian Gieger, Mariaelisa Graff, Leanne M. Hall, Toomas Haller, Fernando Pires Hartwig, David A. Hillis, Ville Huikari, Nancy L. Heard‐Costa, Christina Holzapfel, Anne Jackson, Åsa Johansson, Anja Moltke Jørgensen, Marika Kaakinen, Robert Karlsson, Kathleen F. Kerr, Boram Kim, Chantal M. Koolhaas, Zoltán Kutalik, Vasiliki Lagou, Penelope A. Lind, Mattias Lorentzon, Leo‐Pekka Lyytikäinen, Massimo Mangino, Christoph Metzendorf, Kristine R. Monroe, Alexander Pacolet, Louis Përusse, René Pool, Rebecca C. Richmond, Natalia V. Rivera, Sébastien Robiou-du-Pont, Katharina E. Schraut, Christina‐Alexandra Schulz, Heather M. Stringham, Toshiko Tanaka, Alexander Teumer, Constance Turman, Peter J. van der Most, Mathias Vanmunster, Frank J.A. van Rooij, Jana V. van Vliet‐Ostaptchouk, Xiaoshuai Zhang, Jinghua Zhao, Wei Zhao, Zhanna Balkhiyarova, Marie Balslev‐Harder, Sebastian E. Baumeister, John Beilby, John Blangero, Dorret I. Boomsma, Søren Brage, Peter S. Braund, Jennifer A. Brody, Marcel Bruinenberg, Ulf Ekelund, Ching‐Ti Liu, John W. Cole, Francis S. Collins, L. Adrienne Cupples, Tõnu Esko, Stefan Enroth, Jessica D. Faul, Lindsay Fernández‐Rhodes, Alison E. Fohner, Oscar H. Franco, Tessel E. Galesloot, Scott D. Gordon, Niels Grarup, Catharina A. Hartman, Gerardo Heiss, Jennie Hui, Thomas Illig, Russell Jago, Peter K. Joshi, Taeyeong Jung, Mika Kähönen, Tuomas O. Kilpeläinen, Woon‐Puay Koh, Ivana Kolčić, Peter Kraft, Johanna Kuusisto, Lenore J. Launer, Aihua Li, Allan Linneberg, Jian’an Luan, Pedro Marques‐Vidal, Sarah E. Medland, Yuri Milaneschi, Arden Moscati, Bill Musk, Christopher P. Nelson, Ilja M. Nolte, Nancy L. Pedersen, Annette Peters, Patricia A. Peyser, Christopher Power, Olli T. Raitakari, Mägi Reedik, Alex P. Reiner, Paul M. Ridker, Igor Rudan, Mark A. Sarzynski, Laura J. Scott, Robert A. Scott, Stephen Sidney, Kristín Siggeirsdóttir, Albert V. Smith, Jennifer A. Smith, Emily Sonestedt, Marin Strøm, E Shyong Tai, Koon Teo, Barbara Thorand, Anke Tönjes, Angelo Tremblay, André G. Uitterlinden, Jagadish Vangipurapu, Natasja M. van Schoor, Uwe Völker, Gonneke Willemsen, Kayleen Williams, Quenna Wong, Huichun Xu, Kristin L. Young, Jian‐Min Yuan, M. Carola Zillikens, Alan B. Zonderman, Adam Ameur, Stefania Bandinelli, Joshua C. Bis, Michael Boehnke, Claude Bouchard, Daniel I. Chasman, George Davey Smith, Eco J. C. de Geus, Louise Deldicque, Marcus Dörr, Michele K. Evans, Luigi Ferrucci, Myriam Fornage, Caroline S. Fox, Theodore Garland, Vilmundur Guðnason, Ulf Gyllensten, Torben Hansen, Caroline Hayward, Bernardo Lessa Horta, Elina Hyppönen, Marjo‐Riitta Järvelin, W. Craig Johnson, Sharon L. R. Kardia, Lambertus A. Kiemeney, Markku Laakso, Claudia Langenberg, Terho Lehtimäki, Loı̈c Le Marchand, Behrooz Z. Alizadeh, H. Marike Boezen, Lude Franke, Morris A. Swertz, Cisca Wijmenga, Pim van der Harst, Gerjan Navis, Marianne G. Rots, Bruce H. R. Wolffenbuttel, Patrik K. E. Magnusson, Nicholas G. Martin, Mads Melbye, Andres Metspalu, David Meyre, Kari E. North, Claes Ohlsson, Albertine J. Oldehinkel, Marju Orho‐Melander, Guillaume Paré, Taesung Park, Oluf Pedersen, Brenda W.J.H. Penninx, Tune H. Pers, Ozren Polašek, Inga Prokopenko, Charles N. Rotimi, Nilesh J. Samani, Xueling Sim, Harold Snieder, Thorkild I. A. Sørensen, Tim D. Spector, Nicholas J. Timpson, Rob M. van Dam, Nathalie van der Velde, Cornelia M. van Duijn, Péter Vollenweider, Henry Völzke, Trudy Voortman, Gérard Waeber, Nicholas J. Wareham, David R. Weir, Heinz‐Erich Wichmann, James F. Wilson, Andrea L. Hevener, Anna Krook, Juleen R. Zierath, Martine Thomis, Ruth J. F. Loos, Marcel den Hoed

Bibliographic record

VenueNature Genetics · 2022
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsImpactUniversité LavalMcMaster University
FundersNational Institute of Neurological Disorders and StrokeNational Institute of Diabetes and Digestive and Kidney DiseasesNational Human Genome Research InstituteNational Heart, Lung, and Blood InstituteNational Institute on AgingHelmholtz Zentrum MünchenStatens Serum InstitutFeinberg School of MedicineNational Institutes of HealthNovo Nordisk Foundation Center for Basic Metabolic ResearchMedical Research CouncilUppsala UniversitetTartu ÜlikoolTechnische Universität MünchenBritish Heart FoundationChina Scholarship CouncilVetenskapsrådetNational Cancer InstituteUniversity College LondonUniversité de LausanneKarolinska InstitutetSeoul National UniversityNorthwestern UniversityGenome Institute of SingaporeNational Research Foundation of KoreaMinistry of Science, ICT and Future PlanningNovo NordiskUniversität GreifswaldHjärt-LungfondenAgency for Science, Technology and ResearchUniversity of SurreyNational Institute for Health and Care ResearchNational Research FoundationUniversity of BristolWellcome TrustCancer Research UKFaculty of Health and Medical Sciences, University of Western AustraliaUniversity of LeicesterKjell och Märta Beijers StiftelseUniversity of MiamiEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentGlaxoSmithKlineUniversidade Federal de PelotasKU LeuvenDuke-NUS Medical SchoolQIMR Berghofer Medical Research InstituteSchool of Public Health, University of MichiganNational Institute of Environmental Health SciencesSchool of Medicine, Boston UniversitySteno Diabetes Center CopenhagenMcMaster UniversityImperial College LondonDet Sundhedsvidenskabelige Fakultet, Københavns UniversitetUniversity of North Carolina at Chapel HillScience for Life LaboratoryNational Science FoundationOak FoundationNovo Nordisk FondenAmerican Heart AssociationUniversity of California, Los AngelesUniversity of WashingtonBrigham and Women's HospitalHeart and Stroke Foundation of CanadaNational Health and Medical Research CouncilOulun YliopistoNIHR Leicester Biomedical Research CentreU.S. Department of Veterans Affairs
KeywordsBiologyGenome-wide association studyAssociation (psychology)DiseaseGeneticsSedentary behaviorGenetic associationComputational biologyPhysical activityGenomeEvolutionary biologyGeneSingle-nucleotide polymorphismGenotypeObesityPsychology

Abstract

fetched live from OpenAlex

Abstract Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type II A muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention.

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)0.002
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: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.004
Threshold uncertainty score0.013

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.003
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0030.001
Bibliometrics0.0030.003
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0020.002
Insufficient payload (model declined to judge)0.0040.002

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 head0.043
GPT teacher head0.377
Teacher spread0.334 · 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 designObservational
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

Citations236
Published2022
Admission routes2
Has abstractyes

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