@article{dc0479cdfc5541bd91cb166970702cb2,
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 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.",
keywords = "APOLIPOPROTEIN-E GENOTYPE, LD SCORE REGRESSION, GENE-EXPRESSION, EXERCISE, COMPLEX, PERFORMANCE, GWAS, HERITABILITY, MORTALITY, FITNESS",
author = "Zhe Wang and Andrew Emmerich and Pillon, {Nicolas J.} and Tim Moore and Daiane Hemerich and Cornelis, {Marilyn C.} and Eugenia Mazzaferro and Siacia Broos and Ahluwalia, {Tarunveer S.} and Bartz, {Traci M.} and Bentley, {Amy R.} and Bielak, {Lawrence F.} and Mike Chong and Chu, {Audrey Y.} and Diane Berry and Rajkumar Dorajoo and Dueker, {Nicole D.} and Elisa Kasbohm and Bjarke Feenstra and Feitosa, {Mary F.} and Christian Gieger and Mariaelisa Graff and Hall, {Leanne M.} and Toomas Haller and Hartwig, {Fernando P.} and Hillis, {David A.} and Ville Huikari and Nancy Heard-Costa and Christina Holzapfel and Jackson, {Anne U.} and Asa Johansson and Jorgensen, {Anja Moltke} and Kaakinen, {Marika A.} and Robert Karlsson and Kerr, {Kathleen F.} and Boram Kim and Koolhaas, {Chantal M.} and Zoltan Kutalik and Alexander Pacolet and Jing-Hua Zhao and Balslev-Harder, {Marie N.} and Niels Grarup and Allan Linneberg and Torben Hansen and Mads Melbye and Oluf Pedersen and Pers, {Tune H.} and Sorensen, {Thorkild I. A.} and Zierath, {Juleen R.} and {Oskari Kilpel{\"a}inen}, Tuomas and Loos, {Ruth J. F.} and {LifeLines Cohort Study}",
year = "2022",
doi = "10.1038/s41588-022-01165-1",
language = "English",
volume = "54",
pages = "1332–1344",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "nature publishing group",
}