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J Psychiatr Res. 2019 Nov;118:9-13. doi: 10.1016/j.jpsychires.2019.08.008. Epub 2019 Aug 16.

A polygenic score for body mass index is associated with depressive symptoms via early life stress: Evidence for gene-environment correlation.

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Laboratory of NeuroGenetics, Department of Psychology & Neuroscience, Duke University, Durham, NC, USA. Electronic address:
Laboratory of NeuroGenetics, Department of Psychology & Neuroscience, Duke University, Durham, NC, USA.


Increasing childhood obesity rates are associated with not only adverse physical, but also mental health outcomes, including depression. These negative outcomes may be caused and/or exacerbated by the bullying and shaming overweight individuals experience. As body mass index (BMI) can be highly heritable, we hypothesized that a genetic risk for higher BMI, will predict higher early life stress (ELS), which in turn will predict higher depressive symptoms in adulthood. Such a process will reflect an evocative gene-environment correlation (rGE) wherein an individual's genetically influenced phenotype evokes a reaction from the environment that subsequently shapes the individual's health. We modeled genetic risk using a polygenic score of BMI derived from a recent large GWAS meta-analysis. Self-reports were used for the assessment of ELS and depressive symptoms in adulthood. The discovery sample consisted of 524 non-Hispanic Caucasian university students from the Duke Neurogenetics Study (DNS; 278 women, mean age 19.78 ± 1.23 years) and the independent replication sample consisted of 5930 white British individuals from the UK biobank (UKB; 3128 women, mean age 62.66 ± 7.38 years). A significant mediation effect was found in the DNS (indirect effect = 0.207, bootstrapped SE = .10, bootstrapped 95% CI: 0.014 to 0.421), and then replicated in the UKB (indirect effect = 0.04, bootstrapped SE = .01, bootstrapped 95% CI: 0.018 to 0.066). Higher BMI polygenic scores predicted higher ELS, which in turn predicted higher depressive symptoms. Our findings suggest that evocative rGE may contribute to weight-related mental health problems and stress the need for interventions that aim to reduce weight bias, specifically during childhood.


Body mass index (BMI); Depression; Early life stress; Gene-environment-correlation (rGE); Obesity; Polygenic score

[Available on 2020-11-01]

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