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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.

Author information

1
Laboratory of NeuroGenetics, Department of Psychology & Neuroscience, Duke University, Durham, NC, USA. Electronic address: reut.avinun@mail.huji.ac.il.
2
Laboratory of NeuroGenetics, Department of Psychology & Neuroscience, Duke University, Durham, NC, USA.

Abstract

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.

KEYWORDS:

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

PMID:
31445318
PMCID:
PMC6745266
[Available on 2020-11-01]
DOI:
10.1016/j.jpsychires.2019.08.008

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