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
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.
KW - Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics
KW - Body Mass Index
KW - Denmark
KW - Exercise
KW - Gene-Environment Interaction
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study
KW - Humans
KW - Multifactorial Inheritance
KW - Russia
KW - Self Report
UR - http://www.scopus.com/inward/record.url?scp=85119050503&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0258748
DO - 10.1371/journal.pone.0258748
M3 - Journal article
C2 - 34662357
SN - 1932-6203
VL - 16
SP - e0258748
JO - PLoS One
JF - PLoS One
IS - 10
M1 - e0258748
ER -