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, SD_age = 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 (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. 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. Impact: The association between genetic risk for elevated BMI and body dissatisfaction in adolescents may be largely explained by phenotypic BMI, indicating a potential pathway through which genetic predisposition influences body image perception. Furthermore, age-specific genetic research is needed to understand the unique influences on health outcomes during adolescence. By identifying BMI as a potential mediator in the association between genetic risk for elevated BMI and body dissatisfaction, the current findings offer insights that could inform interventions targeting body image concerns and mental health in this population.