Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention
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Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention. / 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, Asa; Jorgensen, Anja Moltke; Kaakinen, Marika A.; Karlsson, Robert; Kerr, Kathleen F.; Kim, Boram; Koolhaas, Chantal M.; Kutalik, Zoltan; Pacolet, Alexander; Zhao, Jing-Hua; Balslev-Harder, Marie N.; Grarup, Niels; Linneberg, Allan; Hansen, Torben; Melbye, Mads; Pedersen, Oluf; Pers, Tune H.; Sorensen, Thorkild I. A.; Zierath, Juleen R.; Oskari Kilpeläinen, Tuomas; Loos, Ruth J. F.; LifeLines Cohort Study.
In: Nature Genetics, Vol. 54, 2022, p. 1332–1344.Research output: Contribution to journal › Journal article › peer-review
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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 - Emmerich, Andrew
AU - Pillon, Nicolas J.
AU - Moore, Tim
AU - Hemerich, Daiane
AU - Cornelis, Marilyn C.
AU - Mazzaferro, Eugenia
AU - Broos, Siacia
AU - Ahluwalia, Tarunveer S.
AU - Bartz, Traci M.
AU - Bentley, Amy R.
AU - Bielak, Lawrence F.
AU - Chong, Mike
AU - Chu, Audrey Y.
AU - Berry, Diane
AU - Dorajoo, Rajkumar
AU - Dueker, Nicole D.
AU - Kasbohm, Elisa
AU - Feenstra, Bjarke
AU - Feitosa, Mary F.
AU - Gieger, Christian
AU - Graff, Mariaelisa
AU - Hall, Leanne M.
AU - Haller, Toomas
AU - Hartwig, Fernando P.
AU - Hillis, David A.
AU - Huikari, Ville
AU - Heard-Costa, Nancy
AU - Holzapfel, Christina
AU - Jackson, Anne U.
AU - Johansson, Asa
AU - Jorgensen, Anja Moltke
AU - Kaakinen, Marika A.
AU - Karlsson, Robert
AU - Kerr, Kathleen F.
AU - Kim, Boram
AU - Koolhaas, Chantal M.
AU - Kutalik, Zoltan
AU - Pacolet, Alexander
AU - Zhao, Jing-Hua
AU - Balslev-Harder, Marie N.
AU - Grarup, Niels
AU - Linneberg, Allan
AU - Hansen, Torben
AU - Melbye, Mads
AU - Pedersen, Oluf
AU - Pers, Tune H.
AU - Sorensen, Thorkild I. A.
AU - Zierath, Juleen R.
AU - Oskari Kilpeläinen, Tuomas
AU - Loos, Ruth J. F.
AU - LifeLines Cohort Study
PY - 2022
Y1 - 2022
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 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.Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits.
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 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.Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits.
KW - APOLIPOPROTEIN-E GENOTYPE
KW - LD SCORE REGRESSION
KW - GENE-EXPRESSION
KW - EXERCISE
KW - COMPLEX
KW - PERFORMANCE
KW - GWAS
KW - HERITABILITY
KW - MORTALITY
KW - FITNESS
U2 - 10.1038/s41588-022-01165-1
DO - 10.1038/s41588-022-01165-1
M3 - Journal article
C2 - 36071172
VL - 54
SP - 1332
EP - 1344
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
ER -
ID: 320098455