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

Zhe Wang; Marin Strøm

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

Zhe Wang, Marin Strøm

Deildin fyri heilsu- og sjúkrarøktarvísindi - Faculty of Health Sciences

Research output: Contribution to journal › Article › peer-review

83 Citations (Scopus)

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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 IIA 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.

Original language	English
Pages (from-to)	1332-1344
Number of pages	25
Journal	Nature Genetics
Volume	54
Publication status	Published - Sept 2022

Keywords

disease prevention
public health
physical activity

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Wang Strom Genome-wide association analyses of physicalFinal published version, 6.78 MB

https://www.nature.com/articles/s41588-022-01165-1

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@article{6f3556c3cf924d43be0e50b47f4e15e8,

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

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 physicalactivity 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 IIA muscle fibers, andpossibly 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 = "disease prevention, public health, physical activity",

author = "Zhe Wang and Marin Str{\o}m",

note = "All authors: Zhe Wang 1 Andrew Emmerich 2, Nicolas J. Pillon 3, Tim Moore 4, Daiane Hemerich1, Marilyn C. Cornelis5, Eugenia Mazzaferro6, Siacia Broos7,8, Tarunveer S. Ahluwalia9,10,11, Traci M. Bartz12,13, Amy R. Bentley14, Lawrence F. Bielak15, Mike Chong16, Audrey Y. Chu17,18, Diane Berry19, Rajkumar Dorajoo20,21, Nicole D. Dueker22,23, Elisa Kasbohm24,25, Bjarke Feenstra26,Mary F. Feitosa27, Christian Gieger28, Mariaelisa Graff29, Leanne M. Hall30,31, Toomas Haller32,Fernando P. Hartwig33,34, David A. Hillis35, Ville Huikari36, Nancy Heard-Costa37,38,Christina Holzapfel28,39, Anne U. Jackson40, {\AA}sa Johansson41, Anja Moltke J{\o}rgensen10,Marika A. Kaakinen42,43, Robert Karlsson44, Kathleen F. Kerr13, Boram Kim45, Chantal M. Koolhaas46,Zoltan Kutalik47,48,49, Vasiliki Lagou50, Penelope A. Lind51,52, Mattias Lorentzon53,54,Leo-Pekka Lyytik{\"a}inen55,56, Massimo Mangino57,58, Christoph Metzendorf6, Kristine R. Monroe59,Alexander Pacolet7, Louis P{\'e}russe60,61, Rene Pool62,63, Rebecca C. Richmond64, Natalia V. Rivera65,66,67,Sebastien Robiou-du-Pont68, Katharina E. Schraut69, Christina-Alexandra Schulz70,71,Heather M. Stringham40, Toshiko Tanaka72, Alexander Teumer24,73, Constance Turman74,Peter J. van der Most75, Mathias Vanmunster7 , Frank J. A. van Rooij46,Jana V. van Vliet-Ostaptchouk76,77, Xiaoshuai Zhang78,79, Jing-Hua Zhao80, Wei Zhao15,Zhanna Balkhiyarova43,81,82, Marie N. Balslev-Harder10, Sebastian E. Baumeister24,83, John Beilby84,John Blangero85, Dorret I. Boomsma62,63, Soren Brage78, Peter S. Braund30,31, Jennifer A. Brody12,Marcel Bruinenberg86, Ulf Ekelund87,88, Ching-Ti Liu89, John W. Cole90, Francis S. Collins91,L. Adrienne Cupples37,89, T{\~o}nu Esko32, Stefan Enroth41, Jessica D. Faul92, Lindsay Fernandez-Rhodes93,Alison E. Fohner94, Oscar H. Franco46,95, Tessel E. Galesloot96, Scott D. Gordon51, Niels Grarup10, Catharina A. Hartman97, Gerardo Heiss29, Jennie Hui84,98,99, Thomas Illig100,101, Russell Jago102,Alan James103, Peter K. Joshi69,104, Taeyeong Jung45, Mika K{\"a}h{\"o}nen56,105, Tuomas O. Kilpel{\"a}inen10, Woon-Puay Koh106,107, Ivana Kolcic108, Peter P. Kraft74, Johanna Kuusisto109, Lenore J. Launer110, Aihua Li68, Allan Linneberg111,112, Jian{\textquoteright}an Luan78, Pedro Marques Vidal113, Sarah E. Medland51,114, Yuri Milaneschi115, Arden Moscati1 , Bill Musk99,174, Christopher P. Nelson30,31, Ilja M. Nolte75, Nancy L. Pedersen44, Annette Peters116, Patricia A. Peyser15, Christine Power19, Olli T. Raitakari117,118,119, M{\"a}gi Reedik32, Alex P. Reiner120, Paul M. Ridker17,121, Igor Rudan69, Kathy Ryan122, Mark A. Sarzynski123, Laura J. Scott40, Robert A. Scott78, Stephen Sidney124, Kristin Siggeirsdottir125, Albert V. Smith40,125, Jennifer A. Smith15,92, Emily Sonestedt70, Marin Str{\o}m26,126, E. Shyong Tai127,128,129, Koon K. Teo68,130, Barbara Thorand116, Anke T{\"o}njes131, Angelo Tremblay60,61, Andre G. Uitterlinden132, Jagadish Vangipurapu109, Natasja van Schoor133, Uwe V{\"o}lker73,134, Gonneke Willemsen62,63, Nature Genetics | VOL 54 | September 2022 | 1332–1344 | www.nature.com/naturegenetics 1341 Articles NATurE GEnETICS Kayleen Williams13, Quenna Wong13, Huichun Xu122, Kristin L. Young29, Jian Min Yuan135,136, M. Carola Zillikens132, Alan B. Zonderman137, Adam Ameur 41, Stefania Bandinelli138, Joshua C. Bis 12, Michael Boehnke 40, Claude Bouchard 139, Daniel I. Chasman 17,121, George Davey Smith 34,140, Eco J. C. de Geus 62,63, Louise Deldicque141, Marcus D{\"o}rr 73,142, Michele K. Evans137, Luigi Ferrucci 72, Myriam Fornage 143, Caroline Fox144, Theodore Garland Jr 145, Vilmundur Gudnason125,146, Ulf Gyllensten 41, Torben Hansen 10, Caroline Hayward147, Bernardo L. Horta 33, Elina Hypp{\"o}nen 148,149,150, Marjo-Riitta Jarvelin36,151, W. Craig Johnson 13, Sharon L. R. Kardia15, Lambertus A. Kiemeney 96, Markku Laakso 109, Claudia Langenberg 78,152, Terho Lehtim{\"a}ki 55,56, Loic Le Marchand153, Lifelines Cohort Study*, Patrik K. E. Magnusson 44, Nicholas G. Martin 51, Mads Melbye 154,155,156,112, Andres Metspalu 32, David Meyre 16,68, Kari E. North 29, Claes Ohlsson 157,158, Albertine J. Oldehinkel 97, Marju Orho-Melander 70, Guillaume Pare 16, Taesung Park 45,159, Oluf Pedersen 10, Brenda W. J. H. Penninx115, Tune H. Pers 10, Ozren Polasek 160, Inga Prokopenko 81,82,161, Charles N. Rotimi 14, Nilesh J. Samani30,31, Xueling Sim 127, Harold Snieder 75, Thorkild I. A. S{\o}rensen 10,162, Tim D. Spector 57, Nicholas J. Timpson 163, Rob M. van Dam127,164, Nathalie van der Velde132,165,166, Cornelia M. van Duijn46,167, Peter Vollenweider113, Henry V{\"o}lzke24,73, Trudy Voortman 46, G{\'e}rard Waeber 113, Nicholas J. Wareham 78, David R. Weir 92, Heinz-Erich Wichmann116, James F. Wilson 69,147, Andrea L. Hevener168, Anna Krook 3 , Juleen R. Zierath 3,10,169, Martine A. I. Thomis 8, Ruth J. F. Loos 1,10,170 and Marcel den Hoed 6 ",

year = "2022",

month = sep,

language = "English",

volume = "54",

pages = "1332--1344",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

}

TY - JOUR

T1 - Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention

AU - Wang, Zhe

AU - Strøm, Marin

N1 - All authors: Zhe Wang 1 Andrew Emmerich 2, Nicolas J. Pillon 3, Tim Moore 4, Daiane Hemerich1, Marilyn C. Cornelis5, Eugenia Mazzaferro6, Siacia Broos7,8, Tarunveer S. Ahluwalia9,10,11, Traci M. Bartz12,13, Amy R. Bentley14, Lawrence F. Bielak15, Mike Chong16, Audrey Y. Chu17,18, Diane Berry19, Rajkumar Dorajoo20,21, Nicole D. Dueker22,23, Elisa Kasbohm24,25, Bjarke Feenstra26,Mary F. Feitosa27, Christian Gieger28, Mariaelisa Graff29, Leanne M. Hall30,31, Toomas Haller32,Fernando P. Hartwig33,34, David A. Hillis35, Ville Huikari36, Nancy Heard-Costa37,38,Christina Holzapfel28,39, Anne U. Jackson40, Åsa Johansson41, Anja Moltke Jørgensen10,Marika A. Kaakinen42,43, Robert Karlsson44, Kathleen F. Kerr13, Boram Kim45, Chantal M. Koolhaas46,Zoltan Kutalik47,48,49, Vasiliki Lagou50, Penelope A. Lind51,52, Mattias Lorentzon53,54,Leo-Pekka Lyytikäinen55,56, Massimo Mangino57,58, Christoph Metzendorf6, Kristine R. Monroe59,Alexander Pacolet7, Louis Pérusse60,61, Rene Pool62,63, Rebecca C. Richmond64, Natalia V. Rivera65,66,67,Sebastien Robiou-du-Pont68, Katharina E. Schraut69, Christina-Alexandra Schulz70,71,Heather M. Stringham40, Toshiko Tanaka72, Alexander Teumer24,73, Constance Turman74,Peter J. van der Most75, Mathias Vanmunster7 , Frank J. A. van Rooij46,Jana V. van Vliet-Ostaptchouk76,77, Xiaoshuai Zhang78,79, Jing-Hua Zhao80, Wei Zhao15,Zhanna Balkhiyarova43,81,82, Marie N. Balslev-Harder10, Sebastian E. Baumeister24,83, John Beilby84,John Blangero85, Dorret I. Boomsma62,63, Soren Brage78, Peter S. Braund30,31, Jennifer A. Brody12,Marcel Bruinenberg86, Ulf Ekelund87,88, Ching-Ti Liu89, John W. Cole90, Francis S. Collins91,L. Adrienne Cupples37,89, Tõnu Esko32, Stefan Enroth41, Jessica D. Faul92, Lindsay Fernandez-Rhodes93,Alison E. Fohner94, Oscar H. Franco46,95, Tessel E. Galesloot96, Scott D. Gordon51, Niels Grarup10, Catharina A. Hartman97, Gerardo Heiss29, Jennie Hui84,98,99, Thomas Illig100,101, Russell Jago102,Alan James103, Peter K. Joshi69,104, Taeyeong Jung45, Mika Kähönen56,105, Tuomas O. Kilpeläinen10, Woon-Puay Koh106,107, Ivana Kolcic108, Peter P. Kraft74, Johanna Kuusisto109, Lenore J. Launer110, Aihua Li68, Allan Linneberg111,112, Jian’an Luan78, Pedro Marques Vidal113, Sarah E. Medland51,114, Yuri Milaneschi115, Arden Moscati1 , Bill Musk99,174, Christopher P. Nelson30,31, Ilja M. Nolte75, Nancy L. Pedersen44, Annette Peters116, Patricia A. Peyser15, Christine Power19, Olli T. Raitakari117,118,119, Mägi Reedik32, Alex P. Reiner120, Paul M. Ridker17,121, Igor Rudan69, Kathy Ryan122, Mark A. Sarzynski123, Laura J. Scott40, Robert A. Scott78, Stephen Sidney124, Kristin Siggeirsdottir125, Albert V. Smith40,125, Jennifer A. Smith15,92, Emily Sonestedt70, Marin Strøm26,126, E. Shyong Tai127,128,129, Koon K. Teo68,130, Barbara Thorand116, Anke Tönjes131, Angelo Tremblay60,61, Andre G. Uitterlinden132, Jagadish Vangipurapu109, Natasja van Schoor133, Uwe Völker73,134, Gonneke Willemsen62,63, Nature Genetics | VOL 54 | September 2022 | 1332–1344 | www.nature.com/naturegenetics 1341 Articles NATurE GEnETICS Kayleen Williams13, Quenna Wong13, Huichun Xu122, Kristin L. Young29, Jian Min Yuan135,136, M. Carola Zillikens132, Alan B. Zonderman137, Adam Ameur 41, Stefania Bandinelli138, Joshua C. Bis 12, Michael Boehnke 40, Claude Bouchard 139, Daniel I. Chasman 17,121, George Davey Smith 34,140, Eco J. C. de Geus 62,63, Louise Deldicque141, Marcus Dörr 73,142, Michele K. Evans137, Luigi Ferrucci 72, Myriam Fornage 143, Caroline Fox144, Theodore Garland Jr 145, Vilmundur Gudnason125,146, Ulf Gyllensten 41, Torben Hansen 10, Caroline Hayward147, Bernardo L. Horta 33, Elina Hyppönen 148,149,150, Marjo-Riitta Jarvelin36,151, W. Craig Johnson 13, Sharon L. R. Kardia15, Lambertus A. Kiemeney 96, Markku Laakso 109, Claudia Langenberg 78,152, Terho Lehtimäki 55,56, Loic Le Marchand153, Lifelines Cohort Study*, Patrik K. E. Magnusson 44, Nicholas G. Martin 51, Mads Melbye 154,155,156,112, Andres Metspalu 32, David Meyre 16,68, Kari E. North 29, Claes Ohlsson 157,158, Albertine J. Oldehinkel 97, Marju Orho-Melander 70, Guillaume Pare 16, Taesung Park 45,159, Oluf Pedersen 10, Brenda W. J. H. Penninx115, Tune H. Pers 10, Ozren Polasek 160, Inga Prokopenko 81,82,161, Charles N. Rotimi 14, Nilesh J. Samani30,31, Xueling Sim 127, Harold Snieder 75, Thorkild I. A. Sørensen 10,162, Tim D. Spector 57, Nicholas J. Timpson 163, Rob M. van Dam127,164, Nathalie van der Velde132,165,166, Cornelia M. van Duijn46,167, Peter Vollenweider113, Henry Völzke24,73, Trudy Voortman 46, Gérard Waeber 113, Nicholas J. Wareham 78, David R. Weir 92, Heinz-Erich Wichmann116, James F. Wilson 69,147, Andrea L. Hevener168, Anna Krook 3 , Juleen R. Zierath 3,10,169, Martine A. I. Thomis 8, Ruth J. F. Loos 1,10,170 and Marcel den Hoed 6

PY - 2022/9

Y1 - 2022/9

N2 - 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 physicalactivity 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 IIA muscle fibers, andpossibly 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.

AB - 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 physicalactivity 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 IIA muscle fibers, andpossibly 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.

KW - disease prevention

KW - public health

KW - physical activity

M3 - Article

SN - 1061-4036

VL - 54

SP - 1332

EP - 1344

JO - Nature Genetics

JF - Nature Genetics

ER -

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

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Keywords

UN SDGs

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