Lifestyle Modifies the Diabetes-Related Metabolic Risk, Conditional on Individual Genetic Differences
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Date
2022
Authors
Shin, J.
Zhou, X.
Tan, J.T.M.
Hyppönen, E.
Benyamin, B.
Lee, S.H.
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Frontiers in Genetics, 2022; 13:759309-1-759309-10
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Jisu Shin, Xuan Zhou, Joanne T. M. Tan, Elina Hyppönen, Beben Benyamin, and S. Hong Lee
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Abstract
Metabolic syndrome is a group of heritable metabolic traits that are highly associated with type 2 diabetes (T2DM). Classical interventions to T2DM include individual selfmanagement of environmental risk factors, such as improving diet quality, increasing physical activity, and reducing smoking and alcohol consumption, which decreases the risk of developing metabolic syndrome. However, it is poorly understood how the phenotypes of diabetes-related metabolic traits change with respect to lifestyle modifications at the individual level. In the analysis, we used 12 diabetes-related metabolic traits and eight lifestyle covariates from the UK Biobank comprising 288,837 white British participants genotyped for 1,133,273 genome-wide single nucleotide polymorphisms. We found 16 GxE interactions. Modulation of genetic effects by physical activity was seen for four traits (glucose, HbA1c, C-reactive protein, systolic blood pressure) and by alcohol and smoking for three (BMI, glucose, waist–hip ratio and BMI and diastolic and systolic blood pressure, respectively). We also found a number of significant phenotypic modulations by the lifestyle covariates, which were not attributed to the genetic effects in the model. Overall, modulation in the metabolic risk in response to the level of lifestyle covariates was clearly observed, and its direction and magnitude were varied depending on individual differences. We also showed that the metabolic risk inferred by our model was notably higher in T2DM prospective cases than controls. Our findings highlight the importance of individual genetic differences in the prevention and management of diabetes and suggest that the one-size-fits-all approach may not benefit all.
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© 2022 Shin, Zhou, Tan, Hyppönen, Benyamin and Lee. This is an openaccess article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.