Role of polygenic risk in susceptibility to accelerated pubertal onset following chronic stress exposure

in European Journal of Endocrinology
Correspondence should be addressed to Y Sun; Email: yingsun@ahmu.edu.cn
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Objective

Previous finding suggests that children growing up under chronic stress tend to experience earlier sexual maturity. The present study aims to examine polygenic risk by experience interaction in predicting pubertal timing, as well as provide insight regarding the relevance of two G × E paradigms.

Design and methods

Data were analyzed from a 3-year prospective puberty cohort in Anhui Province, China. Breast Tanner stage and testicular volume (TV) of 997 children were annually assessed. The polygenic risk score (PRS) was computed based on 17 SNPs for early pubertal timing. Hair cortisol concentrations (HCC) were assessed in the first 3 cm hair segment as a biological marker of chronic stress.

Results

Comparing with participants under moderate levels of stress as measured by HCC, the puberty-accelerating effects of chronic stress were only observed among girls with moderate (1.7 months earlier, P = 0.007) and low genetic susceptibility (2.2 months earlier, P < 0.001) and among boys with high genetic susceptibility (2.0 months earlier, P = 0.005). Polygenic differences (PRSs) in age at thelarche was most prominent in those with low levels of stress by HCC (9.06, 9.36 and 9.53 years for high, moderate and low PRS, respectively; F = 105.06, P < 0.0001), while polygenic differences in age at TV ≥4 mL was strongest in those under chronic stress (10.91, 11.06 and 11.17 years for high, moderate and low PRS, respectively; F = 100.48, P < 0.0001).

Conclusion

Chronic stress predicts earlier age at pubertal onset in a sex-specific and genetic background-dependent manner. The bioecological G × E model for girls and diathesis stress model for boys in pubertal timing warrants further investigation.

Downloadable materials

  • Supplementary Table 1 Estimates of heterogeneity between ours and study from Elks and Day et al.

 

     European Society of Endocrinology

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Figures

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    Flowchart of this study. A full colour version of this figure is available at https://doi.org/10.1530/EJE-19-0033.

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    Comparing the adjusted likelihood of thelarche (left) and testicular volume ≥4 mL (right) among different chronic stress environment for high, moderate and low genetic risk girls and boys. A full colour version of this figure is available at https://doi.org/10.1530/EJE-19-0033.

  • View in gallery

    Comparing the age at thelarche (left) and testicular volume (TV) ≥ 4 mL (right) by PRS tertiles under adverse (highest tertile of HCC) and favorable (lowest tertile of HCC) environment. *P < 0.05; **P < 0.01; ***P < 0.001. HCC, hair cortisol concentration; PRS, polygenic risk score. A full colour version of this figure is available at https://doi.org/10.1530/EJE-19-0033.

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