Associations between polygenic risk scores for cardiometabolic phenotypes and adolescent depression and body dissatisfaction

Background: Adolescents with elevated body mass index (BMI) are at an increased risk for depression and body dissatisfaction. Type 2 diabetes (T2D) is an established risk factor for depression. However, shared genetic risk between cardiometabolic conditions and mental health outcomes remains understudied in youth. Methods: The current study examined associations between polygenic risk scores (PRS) for BMI and T2D, and symptoms of depression and body dissatisfaction, in a sample of 827 community adolescents (M-age = 13.63, SDage = 1.01; 76% girls). BMI, depressive symptoms, and body dissatisfaction were assessed using validated self-report questionnaires. Results: BMI-PRS was associated with phenotypic BMI (beta = 0.24, p < 0.001) and body dissatisfaction (beta = 0.17, p < 0.001), but not with depressive symptoms. The association between BMI-PRS and body dissatisfaction was significantly mediated by BMI (indirect effect = 0.10, CI [0.07-0.13]). T2D-PRS was not associated with depression or body dissatisfaction. Conclusions: The results suggest phenotypic BMI may largely explain the association between genetic risk for elevated BMI and body dissatisfaction in adolescents. Further research on age-specific genetic effects is needed, as summary statistics from adult discovery samples may have limited utility in youth.