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Wang, Z.* ; Emmerich, A.* ; Pillon, N.J.* ; Moore, T.* ; Hemerich, D.* ; Cornelis, M.C.* ; Mazzaferro, E.* ; Broos, S.* ; Ahluwalia, T.S.* ; Bartz, T.M.* ; Bentley, A.R.* ; Bielak, L.F.* ; Chong, M.* ; Chu, A.Y.* ; Berry, D.* ; Dorajoo, R.* ; Dueker, N.D.* ; Kasbohm, E.* ; Feenstra, B.* ; Feitosa, M.F.* ; Gieger, C. ; Graff, M.* ; Hall, L.M.* ; Haller, T.* ; Hartwig, F.P.* ; Hillis, D.A.* ; Huikari, V.* ; Heard-Costa, N.* ; Holzapfel, C. ; Jackson, A.U.* ; Johansson, Å* ; Jørgensen, A.M.* ; Kaakinen, M.A.* ; Karlsson, R.* ; Kerr, K.F.* ; Kim, B.* ; Koolhaas, C.M.* ; Kutalik, Z.* ; Lagou, V.* ; Lind, P.A.* ; Lorentzon, M.* ; Lyytikäinen, L.P.* ; Mangino, M.* ; Metzendorf, C.* ; Monroe, K.R.* ; Pacolet, A.* ; Perusse, L.* ; Pool, R.* ; Richmond, R.C.* ; Rivera, N.V.* ; Robiou-du-Pont, S.* ; Schraut, K.E.* ; Schulz, C.A.* ; Stringham, H.M.* ; Tanaka, T.* ; Teumer, A.* ; Turman, C.* ; van der Most, P.J.* ; Vanmunster, M.* ; van Rooij, F.J.A.* ; van Vliet-Ostaptchouk, J.V.* ; Zhang, X.* ; Zhao, J.H.* ; Zhao, W.* ; Balkhiyarova, Z.* ; Balslev-Harder, M.N.* ; Baumeister, S.E.* ; Beilby, J.* ; Blangero, J.* ; Boomsma, D.I.* ; Brage, S.* ; Braund, P.S.* ; Brody, J.A.* ; Bruinenberg, M.* ; Ekelund, U.* ; Liu, C.T.* ; Cole, J.W.* ; Collins, F.S.* ; Cupples, L.A.* ; Esko, T.* ; Enroth, S.* ; Faul, J.D.* ; Fernandez-Rhodes, L.* ; Fohner, A.E.* ; Franco, O.H.* ; Galesloot, T.E.* ; Gordon, S.D.* ; Grarup, N.* ; Hartman, C.A.* ; Heiss, G.* ; Hui, J.* ; Illig, T.* ; Jago, R.* ; James, A.* ; Joshi, P.K.* ; Jung, T.* ; Kähönen, M.* ; Kilpeläinen, T.O.* ; Koh, W.P.* ; Kolcic, I.* ; Kraft, P.P.* ; Kuusisto, J.* ; Launer, L.J.* ; Li, A.* ; Linneberg, A.* ; Luan, J.* ; Vidal, P.M.* ; Medland, S.E.* ; Milaneschi, Y.* ; Moscati, A.* ; Musk, B.* ; Nelson, C.P.* ; Nolte, I.M.* ; Pedersen, N.L.* ; Peters, A. ; Peyser, P.A.* ; Power, C.* ; Raitakari, O.T.* ; Reedik, M.* ; Reiner, A.P.* ; Ridker, P.M.* ; Rudan, I.* ; Ryan, K.* ; Sarzynski, M.A.* ; Scott, L.J.* ; Scott, R.A.* ; Sidney, S.* ; Siggeirsdottir, K.* ; Smith, A.V.* ; Smith, J.A.* ; Sonestedt, E.* ; Strøm, M.* ; Tai, E.S.* ; Teo, K.K.* ; Thorand, B. ; Tönjes, A.* ; Tremblay, A.* ; Uitterlinden, A.G.* ; Vangipurapu, J.* ; van Schoor, N.M.* ; Völker, U.* ; Willemsen, G.* ; Williams, K.* ; Wong, Q.* ; Xu, H.* ; Young, K.L.* ; Yuan, J.M.* ; Zillikens, M.C.* ; Zonderman, A.B.* ; Ameur, A.* ; Bandinelli, S.* ; Bis, J.C.* ; Boehnke, M.* ; Bouchard, C.* ; Chasman, D.I.* ; Smith, G.D.* ; de Geus, E.J.C.* ; Deldicque, L.* ; Dörr, M.* ; Evans, M.K.* ; Ferrucci, L.* ; Fornage, M.* ; Fox, C.* ; Garland, T.* ; Gudnason, V.* ; Gyllensten, U.* ; Hansen, T.* ; Hayward, C.* ; Horta, B.L.* ; Hyppönen, E.* ; Jarvelin, M.R.* ; Johnson, W.C.* ; Kardia, S.L.R.* ; Kiemeney, L.A.* ; Laakso, M.* ; Langenberg, C.* ; Lehtimäki, T.* ; Marchand, L.L.* ; Magnusson, P.K.E.* ; Martin, N.G.* ; Melbye, M.* ; Metspalu, A.* ; Meyre, D.* ; North, K.E.* ; Ohlsson, C.* ; Oldehinkel, A.J.* ; Orho-Melander, M.* ; Paré, G.* ; Park, T.* ; Pedersen, O.* ; Penninx, B.W.J.H.* ; Pers, T.H.* ; Polasek, O.* ; Prokopenko, I.* ; Rotimi, C.N.* ; Samani, N.J.* ; Sim, X.* ; Snieder, H.* ; Sørensen, T.I.A.* ; Spector, T.D.* ; Timpson, N.J.* ; van Dam, R.M.* ; van der Velde, N.* ; van Duijn, C.M.* ; Vollenweider, P.* ; Völzke, H.* ; Voortman, T.* ; Waeber, G.* ; Wareham, N.J.* ; Weir, D.R.* ; Wichmann, H.-E. ; Wilson, J.F.* ; Hevener, A.L.* ; Krook, A.* ; Zierath, J.R.* ; Thomis, M.A.I.* ; Loos, R.J.F.* ; Hoed, M.D.*

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

Nat. Genet. 54, 1332–1344 (2022)

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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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

ISSN (print) / ISBN 1061-4036

e-ISSN 1546-1718

Journal Nature Genetics

Quellenangaben Volume: 54, Pages: 1332–1344

Publisher Nature Publishing Group

Publishing Place New York, NY

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Epidemiology II (EPI2)
Institute of Epidemiology (EPI)

Grants Uppsala University