Bidirectional Evidence of Causality for the Association between Higher Sedentary Time and Higher Adiposity
by Mie Tomzak
Photo: Ricky John Molloy
It is commonly accepted that physical inactivity has an effect on body weight and fat tissue, but the causality between body weight and physical inactivity has not been assessed in clinical trials given the long follow-up duration needed, and the ethical issues associated with conducting such a trial. DDA-funded Germán Carrasquilla and his colleagues recently had an article published in eLife, presenting evidence for a bidirectional causality between sedentary time and BMI.
Germán Carrasquilla is a medical doctor and PhD. He works as an assistant professor at the Novo Nordisk Foundation for Basic Metabolic Research. In 2019, he received a grant from the Danish Diabetes Academy. During his postdoctoral fellowship at the University of Copenhagen, he has worked on various projects related to the genetic regulation of weight gain and cardiometabolic risk, and how lifestyle factors play a causal role.
A ‘chicken and egg’ discussion
Germán Carrasquilla is the lead author of the article ‘Mendelian randomization suggests a directional, causal relationship between physical inactivity and adiposity’, published in eLife. The article is co-written by Mario García Ureña, Tove Fall, Thorkild I.A. Sørensen and Tuomas O. Kilpeläinen.
It may seem obvious that inactivity is associated with a higher amount of tissue, so we asked Germán why a study like this and its finds are important.
“This is a very relevant question as it is well accepted that physical inactivity influences body weight, however from a clinical point of view the causality from increased body weight to physical inactivity has not to date been assessed in clinical trials, likely due to the ethical and practical limitations of performing such a study. What we are trying to answer here is the chicken and egg discussion, so what precedes the other. Thus, this study provides bidirectional evidence of causality for the association between higher sedentary time and higher adiposity. This means that decreasing sedentary time is beneficial for weight management, but also that weight loss may help reduce sedentary time, forming a reinforcing loop”, explains Germán Carrasquilla.
Minimising influence of reverse causality and confounding
In the article, Germán and his co-authors assess genetic liability using results from genom-wide association studies for accelerometer-based physical activity and sedentary time in 91,105 individuals and for body mass index (BMI) in 806,834 individuals. As the name might suggest, an accelerometer is a tool that measures acceleration forces, which, depending on the movement, might be static or dynamic.
“This is a Mendelian randomisation approach that uses genetic variants to estimate the causal effect between a physical inactivity and obesity. Since genotypes are randomly assigned at birth and do not change over the lifetime of an individual, genetic variants associated with sedentariness and obesity can be used to assign individuals according to higher or lower levels of these factors, in a randomised manner. This helps to minimise the influence of reverse causality and confounding reported in previous studies,” says Germán Carrasquilla.
Lifelong preventive programs beneficial
Being aware of our bodies’ need to decrease sedentary time is possibly more important than ever, as our modern working lives include more and more sedentary work. Studies like this that confirm the risk of inactivity, might kick-start new ideas and concepts for how we work and live.
“This bidirectional causal relationship between sedentary time and BMI suggests that reducing sedentary time may help reduce BMI, but also that reducing BMI may lead to additional health benefits by helping to reduce sedentary time. Our findings support the view that lifelong preventive programs to reduce sedentary time are beneficial for weight management, and may help in motivating sedentary individuals to follow a more active lifestyle,” says Germán Carrasquilla.
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READ THE ARTICLE HERE:
‘Mendelian randomization suggests a directional, causal relationship between physical inactivity and adiposity’
Germán D. Carrasquilla, Mario García Ureña, Tove Fall, Thorkild I.A. Sørensen & Tuomas O. Kilpeläinen
eLife 2022;11:e70386: Mendelian randomization suggests a bidirectional, causal relationship between physical inactivity and adiposity | eLife (elifesciences.org)
Published 7 March 2022
CONTACT DETAILS:
Germán D. Carrasquilla
Assistant professor, Novo Nordisk Foundation for Basic Metabolic Research
Germán Darío Carrasquilla (0000-0002-7147-9421) (orcid.org)
Email: german.carrasquilla@sund.ku.dk