1. Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention.
- Author
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Wang Z, Emmerich A, Pillon NJ, Moore T, Hemerich D, Cornelis MC, Mazzaferro E, Broos S, Ahluwalia TS, Bartz TM, Bentley AR, Bielak LF, Chong M, Chu AY, Berry D, Dorajoo R, Dueker ND, Kasbohm E, Feenstra B, Feitosa MF, Gieger C, Graff M, Hall LM, Haller T, Hartwig FP, Hillis DA, Huikari V, Heard-Costa N, Holzapfel C, Jackson AU, Johansson Å, Jørgensen AM, Kaakinen MA, Karlsson R, Kerr KF, Kim B, Koolhaas CM, Kutalik Z, Lagou V, Lind PA, Lorentzon M, Lyytikäinen LP, Mangino M, Metzendorf C, Monroe KR, Pacolet A, Pérusse L, Pool R, Richmond RC, Rivera NV, Robiou-du-Pont S, Schraut KE, Schulz CA, Stringham HM, Tanaka T, Teumer A, Turman C, van der Most PJ, Vanmunster M, van Rooij FJA, van Vliet-Ostaptchouk JV, Zhang X, Zhao JH, Zhao W, Balkhiyarova Z, Balslev-Harder MN, Baumeister SE, Beilby J, Blangero J, Boomsma DI, Brage S, Braund PS, Brody JA, Bruinenberg M, Ekelund U, Liu CT, Cole JW, Collins FS, Cupples LA, Esko T, Enroth S, Faul JD, Fernandez-Rhodes L, Fohner AE, Franco OH, Galesloot TE, Gordon SD, Grarup N, Hartman CA, Heiss G, Hui J, Illig T, Jago R, James A, Joshi PK, Jung T, Kähönen M, Kilpeläinen TO, Koh WP, Kolcic I, Kraft PP, Kuusisto J, Launer LJ, Li A, Linneberg A, Luan J, Vidal PM, Medland SE, Milaneschi Y, Moscati A, Musk B, Nelson CP, Nolte IM, Pedersen NL, Peters A, Peyser PA, Power C, Raitakari OT, Reedik M, Reiner AP, Ridker PM, Rudan I, Ryan K, Sarzynski MA, Scott LJ, Scott RA, Sidney S, Siggeirsdottir K, Smith AV, Smith JA, Sonestedt E, Strøm M, Tai ES, Teo KK, Thorand B, Tönjes A, Tremblay A, Uitterlinden AG, Vangipurapu J, van Schoor N, Völker U, Willemsen G, Williams K, Wong Q, Xu H, Young KL, Yuan JM, Zillikens MC, Zonderman AB, Ameur A, Bandinelli S, Bis JC, Boehnke M, Bouchard C, Chasman DI, Smith GD, de Geus EJC, Deldicque L, Dörr M, Evans MK, Ferrucci L, Fornage M, Fox C, Garland T Jr, Gudnason V, Gyllensten U, Hansen T, Hayward C, Horta BL, Hyppönen E, Jarvelin MR, Johnson WC, Kardia SLR, Kiemeney LA, Laakso M, Langenberg C, Lehtimäki T, Marchand LL, Magnusson PKE, Martin NG, Melbye M, Metspalu A, Meyre D, North KE, Ohlsson C, Oldehinkel AJ, Orho-Melander M, Pare G, Park T, Pedersen O, Penninx BWJH, Pers TH, Polasek O, Prokopenko I, Rotimi CN, Samani NJ, Sim X, Snieder H, Sørensen TIA, Spector TD, Timpson NJ, van Dam RM, van der Velde N, van Duijn CM, Vollenweider P, Völzke H, Voortman T, Waeber G, Wareham NJ, Weir DR, Wichmann HE, Wilson JF, Hevener AL, Krook A, Zierath JR, Thomis MAI, Loos RJF, and Hoed MD
- Subjects
- Actinin genetics, Cross-Sectional Studies, Exercise physiology, Humans, Leisure Activities, Genome-Wide Association Study, Sedentary Behavior
- 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
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., (© 2022. The Author(s).)- Published
- 2022
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