Weighing the Genetic Risk: Associations Between Polygenic Risk Scores for Cardiometabolic Phenotypes and Adolescent Depression and Body Dissatisfaction

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. 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 (Mage=13.63, SDage=1.01; 76% girls). BMI, depressive symptoms, and body dissatisfaction were assessed using validated self-report questionnaires. PRS were calculated using summary statistics from the largest genome-wide association studies of BMI and T2D. Analyses included linear regressions and mediation models. BMI-PRS was associated with phenotypic BMI (β=0.24, p<0.001) and body dissatisfaction (β=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. 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.