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Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention.
Wang, Zhe; Emmerich, Andrew; Pillon, Nicolas J; Moore, Tim; Hemerich, Daiane; Cornelis, Marilyn C; Mazzaferro, Eugenia; Broos, Siacia; Ahluwalia, Tarunveer S; Bartz, Traci M; Bentley, Amy R; Bielak, Lawrence F; Chong, Mike; Chu, Audrey Y; Berry, Diane; Dorajoo, Rajkumar; Dueker, Nicole D; Kasbohm, Elisa; Feenstra, Bjarke; Feitosa, Mary F; Gieger, Christian; Graff, Mariaelisa; Hall, Leanne M; Haller, Toomas; Hartwig, Fernando P; Hillis, David A; Huikari, Ville; Heard-Costa, Nancy; Holzapfel, Christina; Jackson, Anne U; Johansson, Åsa; Jørgensen, Anja Moltke; Kaakinen, Marika A; Karlsson, Robert; Kerr, Kathleen F; Kim, Boram; Koolhaas, Chantal M; Kutalik, Zoltan; Lagou, Vasiliki; Lind, Penelope A; Lorentzon, Mattias; Lyytikäinen, Leo-Pekka; Mangino, Massimo; Metzendorf, Christoph; Monroe, Kristine R; Pacolet, Alexander; Pérusse, Louis; Pool, Rene; Richmond, Rebecca C; Rivera, Natalia V.
Affiliation
  • Wang Z; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. zhe.wang@mssm.edu.
  • Emmerich A; Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.
  • Pillon NJ; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
  • Moore T; Division of Cardiology, Department of Medicine, University of California, Los Angeles, CA, USA.
  • Hemerich D; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Cornelis MC; Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
  • Mazzaferro E; The Beijer Laboratory and Department of Immunology, Genetics and Pathology, Uppsala University and SciLifeLab, Uppsala, Sweden.
  • Broos S; Faculty of Movement and Rehabilitation Sciences, Department of Movement Sciences - Exercise Physiology Research Group, KU Leuven, Leuven, Belgium.
  • Ahluwalia TS; Faculty of Movement and Rehabilitation Sciences, Department of Movement Sciences - Physical Activity, Sports & Health Research Group, KU Leuven, Leuven, Belgium.
  • Bartz TM; Steno Diabetes Center Copenhagen, Herlev, Denmark.
  • Bentley AR; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Bielak LF; The Bioinformatics Center, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
  • Chong M; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
  • Chu AY; Department of Biostatistics, University of Washington, Seattle, WA, USA.
  • Berry D; Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
  • Dorajoo R; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
  • Dueker ND; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
  • Kasbohm E; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Feenstra B; GlaxoSmithKline, Cambridge, MA, USA.
  • Feitosa MF; Division of Population, Policy and Practice, Great Ormond Street Hospital Institute for Child Health, University College London, London, UK.
  • Gieger C; Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore.
  • Graff M; Health Services and Systems Research, Duke-NUS Medical School, Singapore, Singapore.
  • Hall LM; John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA.
  • Haller T; Department of Epidemiology & Public Health, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Hartwig FP; Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
  • Hillis DA; Institute of Mathematics and Computer Science, University of Greifswald, Greifswald, Germany.
  • Huikari V; Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
  • Heard-Costa N; Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
  • Holzapfel C; Research Unit of Molecular Epidemiology, Helmholtz Zentrum München -Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Munich, Germany.
  • Jackson AU; Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA.
  • Johansson Å; Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
  • Jørgensen AM; NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK.
  • Kaakinen MA; Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
  • Karlsson R; Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil.
  • Kerr KF; MRC Integrative Epidemiology Unit, NIHR Bristol Biomedical Research Center, University of Bristol, Bristol, UK.
  • Kim B; Genetics, Genomics, and Bioinformatics Graduate Program, University of California, Riverside, CA, USA.
  • Koolhaas CM; Institute of Health Sciences, University of Oulu, Oulu, Finland.
  • Kutalik Z; Framingham Heart Study, Framingham, MA, USA.
  • Lagou V; Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
  • Lind PA; Research Unit of Molecular Epidemiology, Helmholtz Zentrum München -Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Munich, Germany.
  • Lorentzon M; Institute for Nutritional Medicine, School of Medicine, Technical University of Munich, Munich, Germany.
  • Lyytikäinen LP; Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
  • Mangino M; Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
  • Metzendorf C; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Monroe KR; Section of Statistical Multi-omics, Department of Clinical and Experimental Medicine, University of Surrey, Guildford, UK.
  • Pacolet A; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
  • Pérusse L; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Pool R; Department of Biostatistics, University of Washington, Seattle, WA, USA.
  • Richmond RC; Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, South Korea.
  • Rivera NV; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Nat Genet ; 54(9): 1332-1344, 2022 09.
Article in En | MEDLINE | ID: mdl-36071172
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 IIA 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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Genome-Wide Association Study / Sedentary Behavior Type of study: Clinical_trials / Observational_studies / Prevalence_studies / Risk_factors_studies / Systematic_reviews Limits: Humans Language: En Journal: Nat Genet Journal subject: GENETICA MEDICA Year: 2022 Document type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Genome-Wide Association Study / Sedentary Behavior Type of study: Clinical_trials / Observational_studies / Prevalence_studies / Risk_factors_studies / Systematic_reviews Limits: Humans Language: En Journal: Nat Genet Journal subject: GENETICA MEDICA Year: 2022 Document type: Article Affiliation country: United States