Genetic predisposition to high BMI and changes in BMI during adolescence modulate associations between adult BMI and plasma molecules involved in glucose metabolism

Introduction: Glucose metabolism and related blood molecules are strongly associated with adult body mass index (BMI). However, it is unclear whether the magnitude of these associations differs in people whose BMI increased rapidly during adolescence or who have a genetic predisposition to high BMI. Methods: The analyses included 373 Finnish participants (39% males) with BMI data at approximate ages 11.5, 14, 17.5, 22, and 37 years. BMI trajectories (defined as BMI changes (i.e. slope) and BMI baseline (i.e. intercept)) were calculated during adolescence (from 11.5 to 17.5 years of age) using linear mixed-effects (LME) models and adulthood (from ~22 to 37 years of age). We employed LME models to quantify the associations between BMI trajectories during adulthood and nine plasma molecules related to glucose metabolism measured at age ~22 years. For significant associations, we tested whether the levels of the molecules interacted with either changes in BMI during adolescence or a Polygenic Risk Score (PRS) of BMI (PRSBMI). Stratified analyses were performed for men and women. Results: During adulthood, BMI changes per year were 0.16 kg/m2 in men and 0.17 kg/m2 in women. The analysis revealed seven statistically significant associations between plasma molecules with adult BMI, but no associations with weight change during adulthood. Four statistically significant interactions with plasma molecules were identified, all of which were found in women. In predicting BMI at ~22 years old, BMI changes in adolescence interacted positively with glucose (p=2.0e-04) and negatively with citrate levels (p= 5.6e-04), and the PRSBMI interacted positively with glucose (p= 3.4e-04) and negatively with citrate (p= 8.3e-03). Conclusion: The current study provides evidence that PRSBMI and BMI changes during adolescence modulate the associations between BMI during adulthood with glucose and citrate blood levels in women.