Genetic background associated with physically active lifestyle
- Date:
- September 7, 2022
- Source:
- Uppsala University
- Summary:
- Researchers have identified DNA regions that are associated with physical activity or leisure screen time. The findings confirm that physical activity is beneficial for health and suggest that a more sedentary lifestyle can be explained by how muscles respond to exercise.
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In a large international study, researchers at Uppsala University have identified DNA regions that are associated with physical activity or leisure screen time. The findings confirm that physical activity is beneficial for health and suggest that a more sedentary lifestyle can be explained by how muscles respond to exercise.
It is well established that a physically active lifestyle and less time spent sitting are associated with better health. However, trends over time suggest that people in higher income countries are becoming increasingly less active. It is also known from twin and family studies that genetic factors influence physical activity levels, but the biological basis for why some people are more physically active than others remains poorly understood.
To improve our understanding of mechanisms that influence physical activity and its role in disease prevention, researchers from Uppsala University, together with researchers from around the world, combined genetic data from over 700,000 individuals participating in 51 research studies. In doing so, they identified 99 DNA regions that are associated with how much time people report spending on moderate-to-vigorous intensity physical activity or watching a screen during their leisure time.
"We know that people tend to overreport how much time they spend on physical activity, but around half of the DNA regions we identified also show robust associations with physical activity as measured using devices that people wore during daily life. This adds further credibility to our findings," says Ruth Loos from the Novo Nordisk Foundation Center for Basic Metabolic Research, at the University of Copenhagen.
Next, the researchers used DNA variants as instrumental variables and showed that less screen time lowers the risk of obesity. Less screen time and more time spent in moderate-to-vigorous intensity physical activity also protect from diabetes, attention deficit hyperactivity disorder, depression, and earlier age at death.
"We confirmed that physical activity has beneficial effects on health outcomes. We also found that all outcomes that we examined are driven by physical activity's beneficial effect on body mass," says Zhe Wang from Icahn School of Medicine at Mount Sinai in New York and first author of the paper.
Further analyses showed that DNA variants associated with leisure screen time are more often located close to genes whose activity in skeletal muscle is changed by strength training. This suggests that these genes may influence the likelihood of adopting an active lifestyle by affecting the response to training.
The researchers studied one gene in more detail and identified a DNA variant that changes a building block of a protein that is only present in fast-twitch skeletal muscle fibres.
"Our results show that this change results in more elastic muscle fibres that can deliver less force, but are likely less susceptible to exercise-induced muscle damage. We think that this reduced risk of muscle damage after exercise makes it easier for people to have a more active lifestyle," says co-author Andrew Emmerich from the Department of Cell and Molecular Biology, Uppsala University.
In total, the researchers identified 46 genes in the 99 DNA regions that could be relevant for linking genetics and physical activity. The findings suggest that pathways related to locomotion and muscle weakness due to dysfunction of the muscle fibre are probably involved.
"We cannot currently claim that these 46 genes cause someone to be more or less physically active in daily life, but they provide great leads for further studies. Perhaps in the future it will even be possible to trigger the beneficial effects of physical activity without the need to be physically active," says Marcel den Hoed, researcher at the Department of Immunology, Genetics and Pathology at Uppsala University, and lead author of the paper.
Story Source:
Materials provided by Uppsala University. Original written by Linda Koffmar. Note: Content may be edited for style and length.
Journal Reference:
- Zhe Wang, Andrew Emmerich, Nicolas J. Pillon, Tim Moore, Daiane Hemerich, Marilyn C. Cornelis, Eugenia Mazzaferro, Siacia Broos, Tarunveer S. Ahluwalia, Traci M. Bartz, Amy R. Bentley, Lawrence F. Bielak, Mike Chong, Audrey Y. Chu, Diane Berry, Rajkumar Dorajoo, Nicole D. Dueker, Elisa Kasbohm, Bjarke Feenstra, Mary F. Feitosa, Christian Gieger, Mariaelisa Graff, Leanne M. Hall, Toomas Haller, Fernando P. Hartwig, David A. Hillis, Ville Huikari, Nancy Heard-Costa, Christina Holzapfel, Anne U. Jackson, Åsa Johansson, Anja Moltke Jørgensen, Marika A. Kaakinen, Robert Karlsson, Kathleen F. Kerr, Boram Kim, Chantal M. Koolhaas, Zoltan Kutalik, Vasiliki Lagou, Penelope A. Lind, Mattias Lorentzon, Leo-Pekka Lyytikäinen, Massimo Mangino, Christoph Metzendorf, Kristine R. Monroe, Alexander Pacolet, Louis Pérusse, Rene Pool, Rebecca C. Richmond, Natalia V. Rivera, Sebastien 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, Jing-Hua Zhao, Wei Zhao, Zhanna Balkhiyarova, Marie N. Balslev-Harder, Sebastian E. Baumeister, John Beilby, John Blangero, Dorret I. Boomsma, Soren 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 Fernandez-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, Alan James, Peter K. Joshi, Taeyeong Jung, Mika Kähönen, Tuomas O. Kilpeläinen, Woon-Puay Koh, Ivana Kolcic, Peter P. 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, Christine Power, Olli T. Raitakari, Mägi Reedik, Alex P. Reiner, Paul M. Ridker, Igor Rudan, Kathy Ryan, Mark A. Sarzynski, Laura J. Scott, Robert A. Scott, Stephen Sidney, Kristin Siggeirsdottir, Albert V. Smith, Jennifer A. Smith, Emily Sonestedt, Marin Strøm, E. Shyong Tai, Koon K. Teo, Barbara Thorand, Anke Tönjes, Angelo Tremblay, Andre G. Uitterlinden, Jagadish Vangipurapu, Natasja 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 Fox, Theodore Garland, Vilmundur Gudnason, Ulf Gyllensten, Torben Hansen, Caroline Hayward, Bernardo L. Horta, Elina Hyppönen, Marjo-Riitta Jarvelin, W. Craig Johnson, Sharon L. R. Kardia, Lambertus A. Kiemeney, Markku Laakso, Claudia Langenberg, Terho Lehtimäki, Loic Le Marchand, Behrooz Z. Alizadeh, H. Marike Boezen, Lude Franke, Morris Swertz, Cisca Wijmenga, Pim van der Harst, Gerjan Navis, Marianne 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 Pare, Taesung Park, Oluf Pedersen, Brenda W. J. H. Penninx, Tune H. Pers, Ozren Polasek, 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, Peter 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 A. I. Thomis, Ruth J. F. Loos, Marcel den Hoed. Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention. Nature Genetics, 2022; DOI: 10.1038/s41588-022-01165-1
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