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

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.; Pérusse, 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, FJA; 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.; 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, EJC; 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, SLR; Kiemeney, L.A.; Laakso, M.; Langenberg, C.; Lehtimäki, T.; Marchand, L.L.; Magnusson, PKE; Martin, N.G.; Melbye, M.; Metspalu, A.; Meyre, D.; North, K.E.; Ohlsson, C.; Oldehinkel, A.J.; Orho-Melander, M.; Pare, G.; Park, T.; Pedersen, O.; Penninx, BWJH; Pers, T.H.; Polasek, O.; Prokopenko, I.; Rotimi, C.N.; Samani, N.J.; Sim, X.; Snieder, H.; Sørensen, TIA; 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, MAI; Loos, RJF; Hoed, M.D.

doi:10.1038/s41588-022-01165-1

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

Details

Download: 41588_2022_Article_1165.pdf (6940.50 [Ko])
State: Public
Version: Final published version
License: CC BY 4.0

Serval ID

serval:BIB_B7AD437C6019

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

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

Journal

Nature genetics

Author(s)

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., Pérusse 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 FJA, 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., 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 EJC, 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 SLR, Kiemeney L.A., Laakso M., Langenberg C., Lehtimäki T., Marchand L.L., Magnusson PKE, Martin N.G., Melbye M., Metspalu A., Meyre D., North K.E., Ohlsson C., Oldehinkel A.J., Orho-Melander M., Pare G., Park T., Pedersen O., Penninx BWJH, Pers T.H., Polasek O., Prokopenko I., Rotimi C.N., Samani N.J., Sim X., Snieder H., Sørensen TIA, 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 MAI, Loos RJF, Hoed M.D.

Working group(s)

Lifelines Cohort Study

Contributor(s)

Alizadeh B.Z., Boezen H.M., Franke L., Swertz M., Wijmenga C., van der Harst P., Navis G., Rots M., Wolffenbuttel BHR

ISSN

1546-1718 (Electronic)

ISSN-L

1061-4036

Publication state

Published

Issued date

09/2022

Peer-reviewed

Oui

Volume

Number

Pages

1332-1344

Language

english

Notes

Publication types: Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
Publication Status: ppublish

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 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. 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.

Keywords

Actinin/genetics, Cross-Sectional Studies, Exercise/physiology, Genome-Wide Association Study, Humans, Leisure Activities, Sedentary Behavior

URN

urn:nbn:ch:serval-BIB_B7AD437C60195

OAI-PMH

oai:serval.unil.ch:BIB_B7AD437C6019

DOI

10.1038/s41588-022-01165-1

Pubmed

36071172

Web of science

000852469800001