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

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 explai...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8523041/
https://www.ncbi.nlm.nih.gov/pubmed/34662357
http://dx.doi.org/10.1371/journal.pone.0258748
Descripción
Sumario: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 (R(2) = 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/m(2) decrease in BMI in this group, compared to a 0.84 kg/m(2) 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.