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

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, Mike Chong, 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, Alan James, Peter K. Joshi, Taeyeong Jung, Mika Kähönen, Tuomas O. Kilpeläinen, Woon‐Puay Koh, Ivana Kolčić

Nature Genetics · 2022

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Summary

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<sub>A</sub> muscle fibers, and possibly protection from exercise-induced muscle damage. Fi

Source type: Peer-reviewed study
DOI: 10.1038/s41588-022-01165-1
Catalogue ID: SNmois7z1m-90idzf

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