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Non-linear interaction between physical activity and polygenic risk score of body mass index in Danish and Russian populations

Author

Listed:
  • Dmitrii Borisevich
  • Theresia M Schnurr
  • Line Engelbrechtsen
  • Alexander Rakitko
  • Lars Ängquist
  • Valery Ilinsky
  • Mette Aadahl
  • Niels Grarup
  • Oluf Pedersen
  • Thorkild I A Sørensen
  • Torben Hansen

Abstract

Body mass index (BMI) is a highly heritable polygenic trait. It is also affected by various environmental and behavioral risk factors. We used a BMI polygenic risk score (PRS) to study the interplay between the genetic and environmental factors defining BMI. First, we generated a BMI PRS that explained more variance than a BMI genetic risk score (GRS), which was using only genome-wide significant BMI-associated variants (R2 = 13.1% compared to 6.1%). Second, we analyzed interactions between BMI PRS and seven environmental factors. We found a significant interaction between physical activity and BMI PRS, even when the well-known effect of the FTO region was excluded from the PRS, using a small dataset of 6,179 samples. Third, we stratified the study population into two risk groups using BMI PRS. The top 22% of the studied populations were included in a high PRS risk group. Engagement in self-reported physical activity was associated with a 1.66 kg/m2 decrease in BMI in this group, compared to a 0.84 kg/m2 decrease in BMI in the rest of the population. Our results (i) confirm that genetic background strongly affects adult BMI in the general population, (ii) show a non-linear interaction between BMI genetics and physical activity, and (iii) provide a standardized framework for future gene-environment interaction analyses.

Suggested Citation

  • Dmitrii Borisevich & Theresia M Schnurr & Line Engelbrechtsen & Alexander Rakitko & Lars Ängquist & Valery Ilinsky & Mette Aadahl & Niels Grarup & Oluf Pedersen & Thorkild I A Sørensen & Torben Hansen, 2021. "Non-linear interaction between physical activity and polygenic risk score of body mass index in Danish and Russian populations," PLOS ONE, Public Library of Science, vol. 16(10), pages 1-16, October.
    • Handle: RePEc:plo:pone00:0258748
    DOI: 10.1371/journal.pone.0258748
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    1. Tuomas O Kilpeläinen & Lu Qi & Soren Brage & Stephen J Sharp & Emily Sonestedt & Ellen Demerath & Tariq Ahmad & Samia Mora & Marika Kaakinen & Camilla Helene Sandholt & Christina Holzapfel & Christine, 2011. "Physical Activity Attenuates the Influence of FTO Variants on Obesity Risk: A Meta-Analysis of 218,166 Adults and 19,268 Children," PLOS Medicine, Public Library of Science, vol. 8(11), pages 1-14, November.
    2. Anne E. Justice & Thomas W. Winkler & Mary F. Feitosa & Misa Graff & Virginia A. Fisher & Kristin Young & Llilda Barata & Xuan Deng & Jacek Czajkowski & David Hadley & Julius S. Ngwa & Tarunveer S. Ah, 2017. "Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits," Nature Communications, Nature, vol. 8(1), pages 1-19, April.
    3. Mathias Rask-Andersen & Torgny Karlsson & Weronica E Ek & Åsa Johansson, 2017. "Gene-environment interaction study for BMI reveals interactions between genetic factors and physical activity, alcohol consumption and socioeconomic status," PLOS Genetics, Public Library of Science, vol. 13(9), pages 1-20, September.
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