Non-linear interaction between physical activity and polygenic risk score of body mass index in Danish and Russian populations
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Non-linear interaction between physical activity and polygenic risk score of body mass index in Danish and Russian populations. / Borisevich, Dmitrii; Schnurr, Theresia M.; Engelbrechtsen, Line; Rakitko, Alexander; Ängquist, Lars; Ilinsky, Valery; Aadahl, Mette; Grarup, Niels; Pedersen, Oluf; Sørensen, Thorkild I.A.; Hansen, Torben.
In: PLoS ONE, Vol. 16, No. 10, e0258748, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Non-linear interaction between physical activity and polygenic risk score of body mass index in Danish and Russian populations
AU - Borisevich, Dmitrii
AU - Schnurr, Theresia M.
AU - Engelbrechtsen, Line
AU - Rakitko, Alexander
AU - Ängquist, Lars
AU - Ilinsky, Valery
AU - Aadahl, Mette
AU - Grarup, Niels
AU - Pedersen, Oluf
AU - Sørensen, Thorkild I.A.
AU - Hansen, Torben
N1 - Publisher Copyright: Copyright: © 2021 Borisevich et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
U2 - 10.1371/journal.pone.0258748
DO - 10.1371/journal.pone.0258748
M3 - Journal article
C2 - 34662357
AN - SCOPUS:85119050503
VL - 16
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 10
M1 - e0258748
ER -
ID: 285448858