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

LifeLines Cohort Study, Katharina E Schraut, Peter K Joshi, Igor Rudan, Caroline Hayward, James F Wilson

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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 languageEnglish
Article number1332–1344
Pages (from-to)1332-1344
Number of pages25
JournalNature Genetics
Volume54
Issue number9
Early online date7 Sept 2022
DOIs
Publication statusPublished - 7 Sept 2022

Keywords / Materials (for Non-textual outputs)

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

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