학술논문
Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention
Document Type
Article
Author
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.; Robiou-du-Pont, Sebastien; Schraut, Katharina E.; Schulz, Christina-Alexandra; Stringham, Heather M.; Tanaka, Toshiko; Teumer, Alexander; Turman, Constance; van der Most, Peter J.; Vanmunster, Mathias; van Rooij, Frank J. A.; van Vliet-Ostaptchouk, Jana V.; Zhang, Xiaoshuai; Zhao, Jing-Hua; Zhao, Wei; Balkhiyarova, Zhanna; Balslev-Harder, Marie N.; Baumeister, Sebastian E.; Beilby, John; Blangero, John; Boomsma, Dorret I.; Brage, Soren; Braund, Peter S.; Brody, Jennifer A.; Bruinenberg, Marcel; Ekelund, Ulf; Liu, Ching-Ti; Cole, John W.; Collins, Francis S.; Cupples, L. Adrienne; Esko, Tõnu; Enroth, Stefan; Faul, Jessica D.; Fernandez-Rhodes, Lindsay; Fohner, Alison E.; Franco, Oscar H.; Galesloot, Tessel E.; Gordon, Scott D.; Grarup, Niels; Hartman, Catharina A.; Heiss, Gerardo; Hui, Jennie; Illig, Thomas; Jago, Russell; James, Alan; Joshi, Peter K.; Jung, Taeyeong; Kähönen, Mika; Kilpeläinen, Tuomas O.; Koh, Woon-Puay; Kolcic, Ivana; Kraft, Peter P.; Kuusisto, Johanna; Launer, Lenore J.; Li, Aihua; Linneberg, Allan; Luan, Jian’an; Vidal, Pedro Marques; Medland, Sarah E.; Milaneschi, Yuri; Moscati, Arden; Musk, Bill; Nelson, Christopher P.; Nolte, Ilja M.; Pedersen, Nancy L.; Peters, Annette; Peyser, Patricia A.; Power, Christine; Raitakari, Olli T.; Reedik, Mägi; Reiner, Alex P.; Ridker, Paul M.; Rudan, Igor; Ryan, Kathy; Sarzynski, Mark A.; Scott, Laura J.; Scott, Robert A.; Sidney, Stephen; Siggeirsdottir, Kristin; Smith, Albert V.; Smith, Jennifer A.; Sonestedt, Emily; Strøm, Marin; Tai, E. Shyong; Teo, Koon K.; Thorand, Barbara; Tönjes, Anke; Tremblay, Angelo; Uitterlinden, Andre G.; Vangipurapu, Jagadish; van Schoor, Natasja; Völker, Uwe; Willemsen, Gonneke; Williams, Kayleen; Wong, Quenna; Xu, Huichun; Young, Kristin L.; Yuan, Jian Min; Zillikens, M. Carola; Zonderman, Alan B.; Ameur, Adam; Bandinelli, Stefania; Bis, Joshua C.; Boehnke, Michael; Bouchard, Claude; Chasman, Daniel I.; Smith, George Davey; de Geus, Eco J. C.; Deldicque, Louise; Dörr, Marcus; Evans, Michele K.; Ferrucci, Luigi; Fornage, Myriam; Fox, Caroline; Garland, Theodore; Gudnason, Vilmundur; Gyllensten, Ulf; Hansen, Torben; Hayward, Caroline; Horta, Bernardo L.; Hyppönen, Elina; Jarvelin, Marjo-Riitta; Johnson, W. Craig; Kardia, Sharon L. R.; Kiemeney, Lambertus A.; Laakso, Markku; Langenberg, Claudia; Lehtimäki, Terho; Marchand, Loic Le; Magnusson, Patrik K. E.; Martin, Nicholas G.; Melbye, Mads; Metspalu, Andres; Meyre, David; North, Kari E.; Ohlsson, Claes; Oldehinkel, Albertine J.; Orho-Melander, Marju; Pare, Guillaume; Park, Taesung; Pedersen, Oluf; Penninx, Brenda W. J. H.; Pers, Tune H.; Polasek, Ozren; Prokopenko, Inga; Rotimi, Charles N.; Samani, Nilesh J.; Sim, Xueling; Snieder, Harold; Sørensen, Thorkild I. A.; Spector, Tim D.; Timpson, Nicholas J.; van Dam, Rob M.; van der Velde, Nathalie; van Duijn, Cornelia M.; Vollenweider, Peter; Völzke, Henry; Voortman, Trudy; Waeber, Gérard; Wareham, Nicholas J.; Weir, David R.; Wichmann, Heinz-Erich; Wilson, James F.; Hevener, Andrea L.; Krook, Anna; Zierath, Juleen R.; Thomis, Martine A. I.; Loos, Ruth J. F.; Hoed, Marcel den
Source
Nature Genetics; September 2022, Vol. 54 Issue: 9 p1332-1344, 13p
Subject
Language
ISSN
10614036; 15461718
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 ACTN3makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIAmuscle 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.