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Pediatrics

Polygenic differential susceptibility to cumulative stress exposure and childhood obesity

International Journal of Obesity volume 42, pages 1177–1184 (2018)Cite this article

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Abstract

Objective

To examine whether polygenic susceptibility for body mass index (BMI) interacts with cumulative stress exposure, potentially exacerbating and buffering the effects of chronic stress, to predict obesity during childhood.

Methods

Data were analyzed from an established prospective puberty cohort in Anhui province, China. A total of 1000 children (421 boys and 579 girls, mean (standard deviation) age 8.97 (0.86) years) who had complete DNA genotyping, hair cortisol concentration and BMI were eligible for the study. The polygenic susceptibility score (PSS) was computed based on 11 SNPs derived from a published genome-wide association study for child obesity.

Results

Children with different obesity polygenic susceptibility did not differ in BMI, obesogenic behaviors and HCC. The positive association between HCC with BMI was only found among children with highest PSS (r = 0.269, P < 0.001). When exposed in cumulative stress, children with highest PSS have higher BMI (β = 1.46, 95% CI: 0.63, 2.29; P = 0.001) than those having lowest PSS. The reverse pattern was found among children without cumulative stress exposure, those with highest PSS showed lowest BMI (β = −1.27, 95% CI: −2.17, −0.38; P = 0.001), compared to lowest PSS groups. Re-parameterized regression models provide strong support for the differential susceptibility hypothesis.

Conclusions

The findings underlie the importance of shifting perspectives from gene vulnerability to gene plasticity in the field of childhood obesity prevention. Children carrying additional BMI-raising alleles are at heightened risk of obesity are at heightened risk of obesity; however, they seem to be protected against obesity when the adverse psychosocial environment is removed.

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Acknowledgements

We acknowledge funding from the National Natural Science Foundation of China (81673188 for YS), Key Project of Natural Science Foundation of Anhui Education (KJ2016A338 for YS).

Author contributions

Study concept and design: YS, FT. Acquisition, analysis, or interpretation of data: YS, JF, YW, JH, YX, FT. DNA genotype: JF. Hair cortisol extraction: YX, JH. Drafting of the manuscript: Sun. Critical revision of the manuscript for important intellectual content: YS, FT. Statistical analysis: YS, JF. Study supervision: FT.

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Authors and Affiliations

  1. Department of Maternal, Child & Adolescent Health, School of Public Health, Hefei, Anhui Province, China

    Ying Sun, Jiao Fang, Yuhui Wan, Jingjing Hu, Yuanyuan Xu & Fangbiao Tao

  2. Anhui Provincial Key Laboratory of Population Health & Aristogenics, Anhui Medical University, Hefei, Anhui Province, China

    Ying Sun, Jiao Fang, Yuhui Wan, Jingjing Hu, Yuanyuan Xu & Fangbiao Tao

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  1. Ying Sun
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Correspondence to Ying Sun.

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Sun, Y., Fang, J., Wan, Y. et al. Polygenic differential susceptibility to cumulative stress exposure and childhood obesity. Int J Obes 42, 1177–1184 (2018). https://doi.org/10.1038/s41366-018-0116-z

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