Identification of Genetic and Environmental Factors Predicting Metabolically Healthy Obesity in Children: Data From the BCAMS Study

Context: Available data related to the metabolically healthy obesity (MHO) phenotype are mainly derived from studies in adults because studies during childhood are very limited to date. Objective: The objective of the study was to determine the prevalence of MHO in Chinese children and to investigate environmental and genetic factors impacting on MHO status. Design: This was a cross-sectional study. Participants: A total of 1213 children with a body mass index at the 95th percentile or greater aged 6-18 years were included in this study. Participants were classified as MHO or of metabolically unhealthy obesity based on insulin resistance (IR) or cardiometabolic risk (CR) factors (blood pressure, lipids, and glucose). Twenty-two genetic variants previously reported from genome-wide association studies of obesity and diabetes plus the environmental factors of lifestyle, socioeconomic status, and birth weight was assessed. Results: The prevalence of MHO-IR and MHO-CR were 27.1% and 37.2%, respectively. Waist circumference was an independent predictor of MHO, regardless of definitions, whereas walking to school and KCNQ1-rs2237897 were independent predictors of MHO-CR. Acanthosis nigricans, birth weight, the frequency of soft drink consumption, the mother's education status, and KCNQ1-rs2237892 were independent predictors of MHO-IR. Multiplicative interaction effects were found between KCNQ1-rs2237897 and walking to school on MHO-CR (odds ratio 1.31 [95% confidence interval 1.05-1.63]) and between rs2237892 and consumption of soft drinks on MHO-IR (odds ratio 0.80 [95% confidence interval 0.68-0.94]). Conclusions: Approximately one-third of Chinese obese children can be classified as MHO. Both genetic predisposition and environment factors and their interaction contribute to the prediction of MHO status. This study provides novel insights into the heterogeneity of obesity and has the potential to impact the optimization of the intervention options and regimens in the management of pediatric obesity.