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

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Abstract

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 (Mage = 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 (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.

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Fig. 1: Phenotypic BMI mediates the association between BMI-PRS and body dissatisfaction.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We gratefully acknowledge the support of participants in each study for generously contributing their time and efforts.

Funding

Support for this research was provided by funding through NIMH grants R01 MH069942 (D.N.K.), R01 MH093479 (D.N.K. and R.K.), and R56 MH117116 (D.N.K. and R.K.).

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Authors and Affiliations

  1. Department of Psychology, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA

    Krista M. Ekberg, Kristin L. Schneider & Monika A. Waszczuk

  2. Department of Biological and Experimental Psychology, Queen Mary University of London, London, UK

    Giorgia Michelini

  3. Department of Psychiatry, University of Utah, Salt Lake City, UT, USA

    Anna R. Docherty & Andrey A. Shabalin

  4. Department of Psychiatry, Stony Brook University, Stony Brook, NY, USA

    Greg Perlman & Roman Kotov

  5. Department of Psychology, Stony Brook University, Stony Brook, NY, USA

    Daniel N. Klein

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  1. Krista M. Ekberg
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Contributions

Substantial contributions to conception and design: Ekberg, K.M., Waszczuk, M.A.; acquisition of data: Kotov, R., Klein, D.N., Perlman, G.; analysis and interpretation of data: Ekberg, K.M., Waszczuk, M.A.; drafting the article: Ekberg, K.M., Waszczuk, M.A., revising it critically for important intellectual content: Ekberg, K.M., Michelini, G., Schneider, K.L., Waszczuk, M.A., final approval of the version to be published: Ekberg, K.M., Michelini, G., Schneider, K.L., Docherty, A.R., Shabalin, A.A., Perlman, G., Kotov, R., Klein, D.N., Waszczuk, M.A.

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Correspondence to Krista M. Ekberg.

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Ekberg, K.M., Michelini, G., Schneider, K.L. et al. Associations between polygenic risk scores for cardiometabolic phenotypes and adolescent depression and body dissatisfaction. Pediatr Res (2024). https://doi.org/10.1038/s41390-024-03323-z

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