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

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Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention
Nature Genetics ( IF 30.8 ) Pub Date : 2022-09-07 , DOI: 10.1038/s41588-022-01165-1
Zhe Wang ₁ , Andrew Emmerich ₂ , Nicolas J Pillon ₃ , Tim Moore ₄ , Daiane Hemerich ₁ , Marilyn C Cornelis ₅ , Eugenia Mazzaferro ₆ , Siacia Broos _{7,

8} , Tarunveer S Ahluwalia _{9,

10,

11} , Traci M Bartz _{12,

13} , Amy R Bentley ₁₄ , Lawrence F Bielak ₁₅ , Mike Chong ₁₆ , Audrey Y Chu _{17,

18} , Diane Berry ₁₉ , Rajkumar Dorajoo _{20,

21} , Nicole D Dueker _{22,

23} , Elisa Kasbohm _{24,

25} , Bjarke Feenstra ₂₆ , Mary F Feitosa ₂₇ , Christian Gieger ₂₈ , Mariaelisa Graff ₂₉ , Leanne M Hall _{30,

31} , Toomas Haller ₃₂ , Fernando P Hartwig _{33,

34} , David A Hillis ₃₅ , Ville Huikari ₃₆ , Nancy Heard-Costa _{37,

38} , Christina Holzapfel _{28,

39} , Anne U Jackson ₄₀ , Åsa Johansson ₄₁ , Anja Moltke Jørgensen ₁₀ , Marika A Kaakinen _{42,

43} , Robert Karlsson ₄₄ , Kathleen F Kerr ₁₃ , Boram Kim ₄₅ , Chantal M Koolhaas ₄₆ , Zoltan Kutalik _{47,

48,

49} , Vasiliki Lagou ₅₀ , Penelope A Lind _{51,

52} , Mattias Lorentzon _{53,

54} , Leo-Pekka Lyytikäinen _{55,

56} , Massimo Mangino _{57,

58} , Christoph Metzendorf ₆ , Kristine R Monroe ₅₉ , Alexander Pacolet ₇ , Louis Pérusse _{60,

61} , Rene Pool _{62,

63} , Rebecca C Richmond ₆₄ , Natalia V Rivera _{65,

66,

67} , Sebastien Robiou-du-Pont ₆₈ , Katharina E Schraut ₆₉ , Christina-Alexandra Schulz _{70,

71} , Heather M Stringham ₄₀ , Toshiko Tanaka ₇₂ , Alexander Teumer _{24,

73} , Constance Turman ₇₄ , Peter J van der Most ₇₅ , Mathias Vanmunster ₇ , Frank J A van Rooij ₄₆ , Jana V van Vliet-Ostaptchouk _{76,

77} , Xiaoshuai Zhang _{78,

79} , Jing-Hua Zhao ₈₀ , Wei Zhao ₁₅ , Zhanna Balkhiyarova _{43,

81,

82} , Marie N Balslev-Harder ₁₀ , Sebastian E Baumeister _{24,

83} , John Beilby ₈₄ , John Blangero ₈₅ , Dorret I Boomsma _{62,

63} , Soren Brage ₇₈ , Peter S Braund _{30,

31} , Jennifer A Brody ₁₂ , Marcel Bruinenberg ₈₆ , Ulf Ekelund _{87,

88} , Ching-Ti Liu ₈₉ , John W Cole ₉₀ , Francis S Collins ₉₁ , L Adrienne Cupples _{37,

89} , Tõnu Esko ₃₂ , Stefan Enroth ₄₁ , Jessica D Faul ₉₂ , Lindsay Fernandez-Rhodes ₉₃ , Alison E Fohner ₉₄ , Oscar H Franco _{46,

95} , Tessel E Galesloot ₉₆ , Scott D Gordon ₅₁ , Niels Grarup ₁₀ , Catharina A Hartman ₉₇ , Gerardo Heiss ₂₉ , Jennie Hui _{84,

98,

99} , Thomas Illig _{100,

101} , Russell Jago ₁₀₂ , Alan James ₁₀₃ , Peter K Joshi _{69,

104} , Taeyeong Jung ₄₅ , Mika Kähönen _{56,

105} , Tuomas O Kilpeläinen ₁₀ , Woon-Puay Koh _{106,

107} , Ivana Kolcic ₁₀₈ , Peter P Kraft ₇₄ , Johanna Kuusisto ₁₀₉ , Lenore J Launer ₁₁₀ , Aihua Li ₆₈ , Allan Linneberg _{111,

112} , Jian'an Luan ₇₈ , Pedro Marques Vidal ₁₁₃ , Sarah E Medland _{51,

114} , Yuri Milaneschi ₁₁₅ , Arden Moscati ₁ , Bill Musk ₉₉ , Christopher P Nelson _{30,

31} , Ilja M Nolte ₇₅ , Nancy L Pedersen ₄₄ , Annette Peters ₁₁₆ , Patricia A Peyser ₁₅ , Christine Power ₁₉ , Olli T Raitakari _{117,

118,

119} , Mägi Reedik ₃₂ , Alex P Reiner ₁₂₀ , Paul M Ridker _{17,

121} , Igor Rudan ₆₉ , Kathy Ryan ₁₂₂ , Mark A Sarzynski ₁₂₃ , Laura J Scott ₄₀ , Robert A Scott ₇₈ , Stephen Sidney ₁₂₄ , Kristin Siggeirsdottir ₁₂₅ , Albert V Smith _{40,

125} , Jennifer A Smith _{15,

92} , Emily Sonestedt ₇₀ , Marin Strøm _{26,

126} , E Shyong Tai _{127,

128,

129} , Koon K Teo _{68,

130} , Barbara Thorand ₁₁₆ , Anke Tönjes ₁₃₁ , Angelo Tremblay _{60,

61} , Andre G Uitterlinden ₁₃₂ , Jagadish Vangipurapu ₁₀₉ , Natasja van Schoor ₁₃₃ , Uwe Völker _{73,

134} , Gonneke Willemsen _{62,

63} , Kayleen Williams ₁₃ , Quenna Wong ₁₃ , Huichun Xu ₁₂₂ , Kristin L Young ₂₉ , Jian Min Yuan _{135,

136} , M Carola Zillikens ₁₃₂ , Alan B Zonderman ₁₃₇ , Adam Ameur ₄₁ , Stefania Bandinelli ₁₃₈ , Joshua C Bis ₁₂ , Michael Boehnke ₄₀ , Claude Bouchard ₁₃₉ , Daniel I Chasman _{17,

121} , George Davey Smith _{34,

140} , Eco J C de Geus _{62,

63} , Louise Deldicque ₁₄₁ , Marcus Dörr _{73,

142} , Michele K Evans ₁₃₇ , Luigi Ferrucci ₇₂ , Myriam Fornage ₁₄₃ , Caroline Fox ₁₄₄ , Theodore Garland ₁₄₅ , Vilmundur Gudnason _{125,

146} , Ulf Gyllensten ₄₁ , Torben Hansen ₁₀ , Caroline Hayward ₁₄₇ , Bernardo L Horta ₃₃ , Elina Hyppönen _{148,

149,

150} , Marjo-Riitta Jarvelin _{36,

151} , W Craig Johnson ₁₃ , Sharon L R Kardia ₁₅ , Lambertus A Kiemeney ₉₆ , Markku Laakso ₁₀₉ , Claudia Langenberg _{78,

152} , Terho Lehtimäki _{55,

56} , Loic Le Marchand ₁₅₃ , , Patrik K E Magnusson ₄₄ , Nicholas G Martin ₅₁ , Mads Melbye _{112,

154,

155,

156} , Andres Metspalu ₃₂ , David Meyre _{16,

68} , Kari E North ₂₉ , Claes Ohlsson _{157,

158} , Albertine J Oldehinkel ₉₇ , Marju Orho-Melander ₇₀ , Guillaume Pare ₁₆ , Taesung Park _{45,

159} , Oluf Pedersen ₁₀ , Brenda W J H Penninx ₁₁₅ , Tune H Pers ₁₀ , Ozren Polasek ₁₆₀ , Inga Prokopenko _{81,

82,

161} , Charles N Rotimi ₁₄ , Nilesh J Samani _{30,

31} , Xueling Sim ₁₂₇ , Harold Snieder ₇₅ , Thorkild I A Sørensen _{10,

162} , Tim D Spector ₅₇ , Nicholas J Timpson ₁₆₃ , Rob M van Dam _{127,

164} , Nathalie van der Velde _{132,

165,

166} , Cornelia M van Duijn _{46,

167} , Peter Vollenweider ₁₁₃ , Henry Völzke _{24,

73} , Trudy Voortman ₄₆ , Gérard Waeber ₁₁₃ , Nicholas J Wareham ₇₈ , David R Weir ₉₂ , Heinz-Erich Wichmann ₁₁₆ , James F Wilson _{69,

147} , Andrea L Hevener ₁₆₈ , Anna Krook ₃ , Juleen R Zierath _{3,

10,

169} , Martine A I Thomis ₈ , Ruth J F Loos _{1,

10,

170} , Marcel den Hoed ₆

Affiliation

The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Division of Cardiology, Department of Medicine, University of California, Los Angeles, CA, USA.
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
The Beijer Laboratory and Department of Immunology, Genetics and Pathology, Uppsala University and SciLifeLab, Uppsala, Sweden.
Faculty of Movement and Rehabilitation Sciences, Department of Movement Sciences - Exercise Physiology Research Group, KU Leuven, Leuven, Belgium.
Faculty of Movement and Rehabilitation Sciences, Department of Movement Sciences - Physical Activity, Sports & Health Research Group, KU Leuven, Leuven, Belgium.
Steno Diabetes Center Copenhagen, Herlev, Denmark.
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
The Bioinformatics Center, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
Department of Biostatistics, University of Washington, Seattle, WA, USA.
Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.
GlaxoSmithKline, Cambridge, MA, USA.
Division of Population, Policy and Practice, Great Ormond Street Hospital Institute for Child Health, University College London, London, UK.
Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore.
Health Services and Systems Research, Duke-NUS Medical School, Singapore, Singapore.
John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA.
Department of Epidemiology & Public Health, University of Maryland School of Medicine, Baltimore, MD, USA.
Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Institute of Mathematics and Computer Science, University of Greifswald, Greifswald, Germany.
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München -Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Munich, Germany.
Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA.
Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK.
Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil.
MRC Integrative Epidemiology Unit, NIHR Bristol Biomedical Research Center, University of Bristol, Bristol, UK.
Genetics, Genomics, and Bioinformatics Graduate Program, University of California, Riverside, CA, USA.
Institute of Health Sciences, University of Oulu, Oulu, Finland.
Framingham Heart Study, Framingham, MA, USA.
Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
Institute for Nutritional Medicine, School of Medicine, Technical University of Munich, Munich, Germany.
Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Section of Statistical Multi-omics, Department of Clinical and Experimental Medicine, University of Surrey, Guildford, UK.
Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, South Korea.
Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
University Center for Primary Care and Public Health, University of Lausanne, Lausanne, Switzerland.
Swiss Institute of Bioinformatics, Lausanne, Switzerland.
Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
Wellcome Sanger Institute, Cambridge, UK.
Mental Health and Neuroscience Research Program, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
School of Biomedical Science, Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia.
Geriatric Medicine, Institute of Medicine, University of Gothenburg and Sahlgrenska University Hospital Mölndal, Gothenburg, Sweden.
Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, Victoria, Australia.
Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland.
Finnish Cardiovascular Research Center - Tampere, Department of Clinical Chemistry, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Department of Twin Research and Genetic Epidemiology, Kings College London, London, UK.
NIHR Biomedical Research Centre at Guy's and St Thomas' Foundation Trust, London, UK.
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Department of Kinesiology, Université Laval, Quebec, Quebec, Canada.
Centre Nutrition Santé et Société (NUTRISS), Institute of Nutrition and Functional Foods (INAF), Université Laval, Quebec, Quebec, Canada.
Department of Biological Psychology, Vrije Universiteit, Amsterdam, the Netherlands.
Amsterdam Public Health Research Institute, Amsterdam UMC, Amsterdam, the Netherlands.
MRC Integrative Epidemiology Unit and Avon Longitudinal Study of Parents and Children, University of Bristol Medical School, Population Health Sciences and Avon Longitudinal Study of Parents and Children, University of Bristol, Bristol, UK.
Respiratory Division, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Rheumatology Division, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Center of Molecular Medicine (CMM), Karolinska Institutet, Stockholm, Sweden.
Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.
Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, UK.
Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
Department of Nutrition and Food Sciences, Nutritional Epidemiology, University of Bonn, Bonn, Germany.
Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
German Centre for Cardiovascular Research (DZHK), partner site Greifswald, Greifswald, Germany.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
MRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
School of Public Health, Department of Biostatistics, Shandong University, Jinan, China.
Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Department of Clinical and Experimental Medicine, University of Surrey, Guilford, UK.
People-Centred Artificial Intelligence Institute, University of Surrey, Guilford, UK.
University of Münster, Münster, Germany.
Diagnostic Genomics, PathWest Laboratory Medicine WA, Perth, Western Australia, Australia.
South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley, Brownsville, TX, USA.
Lifelines Cohort Study, Groningen, the Netherlands.
Department of Sports Medicine, Norwegian School of Sport Sciences, Oslo, Norway.
Department of Chronic Diseases, Norwegian Institute of Public Health, Oslo, Norway.
Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Vascular Neurology, Department of Neurology, University of Maryland School of Medicine and the Baltimore VAMC, Baltimore, MD, USA.
Center for Precision Health Research, National Human Genome Research Institute, NIH, Bethesda, MD, USA.
Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA.
Department of Biobehavioral Health, College of Health and Human Development, Pennsylvania State University, University Park, PA, USA.
Department of Epidemiology, Institute of Public Health Genetics, Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.
Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland.
Radboud Institute for Health Sciences, Department for Health Evidence, Radboud University Medical Center, Nijmegen, the Netherlands.
Interdisciplinary Center Psychopathology and Emotion Regulation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
School of Population and Global Health, The University of Western Australia, Perth, Western Australia, Australia.
Busselton Population Medical Research Institute, Busselton, Western Australia, Australia.
Hannover Unified Biobank, Hannover Medical School, Hannover, Germany.
Department of Human Genetics, Hannover Medical School, Hannover, Germany.
Centre for Exercise Nutrition & Health Sciences, School for Policy Studies, University of Bristol, Bristol, UK.
Department of Pulmonary Physiology and Sleep Medicine, Sir Charles Gairdner Hospital, Western Australia, Perth, Australia.
Humanity Inc, Boston, MA, USA.
Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland.
Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Singapore Institute for Clinical Sciences, Agency for Science, Technology, and Research, Singapore, Singapore.
Department of Public Health, University of Split School of Medicine, Split, Croatia.
Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
Laboratory of Epidemiology and Population Sciences, National Institutes of Health, Baltimore, MD, USA.
Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Division of Internal Medicine, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
School of Psychology and Faculty of Medicine, University of Queensland, St Lucia, Queensland, Australia.
Department of Psychiatry, Amsterdam UMC, Vrije Universiteit, Amsterdam, the Netherlands.
Institute of Epidemiology, Helmholtz Zentrum München -Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Munich, Germany.
Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland.
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
Department of Epidemiology, University of Washington, Seattle, WA, USA.
Harvard Medical School, Boston, MA, USA.
Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
Department of Exercise Science, University of South Carolina, Columbia, SC, USA.
Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
Icelandic Heart Association, Kópavogur, Iceland.
Faculty of Health Sciences, University of the Faroe Islands, Tórshavn, Faroe Islands.
Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.
Duke-NUS Medical School, Singapore, Singapore.
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Department of Medicine, University of Leipzig, Leipzig, Germany.
Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
Department of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, VU University Medical Center, Amsterdam, the Netherlands.
Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
Division of Cancer Control and Population Sciences, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
Laboratory of Epidemiology and Population Science, National Instiute on Aging, National Institutes of Health, Bethesda, MD, USA.
Geriatric Unit, Azienda USL Toscana Centro, Florence, Italy.
Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA.
Population Health Science, Bristol Medical School, NIHR Bristol Biomedical Research Center, University of Bristol, Bristol, UK.
Faculty of Movement and Rehabilitation Sciences, Institute of Neuroscience, UC Louvain, Louvain-la-Neuve, Belgium.
Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany.
Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Genetics and Pharmacogenomics (GpGx), Merck Research Labs, Boston, MA, USA.
Department of Evolution, Ecology, and Organismal Biology, University of California, Riverside, Riverside, CA, USA.
Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
Australian Centre for Precision Health, Unit of Clinical and Health Sciences, University of South Australia, Adelaide, South Australia, Australia.
South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
Population, Policy and Practice, Great Ormond Street Hospital Institute for Child Health, University College London, London, UK.
Department of Epidemiology and Biostatistics and HPA-MRC Center, School of Public Health, Imperial College London, London, UK.
Computational Medicine, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany.
Epidemiology Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI, USA.
K.G.Jebsen Center for Genetic Epidemiology, Norwegian University of Science and Technology, Trondheim, Norway.
Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
Center for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.
Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Department of Drug Treatment, Sahlgrenska University Hospital, Gothenburg, Sweden.
Department of Statistics, Seoul National University, Seoul, South Korea.
University of Split School of Medicine, Split, Croatia.
UMR 8199 - EGID, Institut Pasteur de Lille, CNRS, University of Lille, Lille, France.
Department of Public Health, Section of Epidemiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
MRC Integrative Epidemiology Unit, University of Bristol Medical School, University of Bristol, Bristol, UK.
Department of Exercise and Nutrition Sciences, Milken Institute School of Public Health, George Washington University, Washington, DC, USA.
Section of Geriatrics, Department of Internal Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Amsterdam Public Health, Aging and Later Life, Amsterdam, the Netherlands.
Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Division of Endocrinology, Department of Medicine, University of California, Los Angeles, CA, USA.
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

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.

中文翻译：

对身体活动和久坐行为的全基因组关联分析提供了对疾病预防中潜在机制和作用的见解

尽管体力活动和久坐行为具有一定的遗传性，但人们对影响这些特征的机制知之甚少。在全基因组关联研究的多祖先荟萃分析中，将来自 51 项研究的多达 703,901 名个体的数据结合起来，得出了 99 个与自我报告的闲暇时间中度至剧烈身体活动 (MVPA)、休闲筛选相关的位点工作时间 (LST) 和/或久坐行为。与 LST 相关的基因座富集了一些基因，这些基因在骨骼肌中的表达会因阻力训练而改变。ACTN3中的错义变体使 α-actinin-3 细丝更加柔韧，从而导致孤立的 II _A型肌纤维的最大力量降低，并可能防止运动引起的肌肉损伤。最后，孟德尔随机化分析表明，较低的 LST 和较高的 MVPA 对多种危险因素和疾病的有益影响是由体重指数 (BMI) 介导或混淆的。我们的研究结果提供了对身体活动机制及其在疾病预防中的作用的见解。

更新日期：2022-09-08

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