慢性应激下多基因遗传风险致青春期发育加速的效应

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

Highlight:首次将多基因风险评分应用到青春期相关遗传和环境交互作用研究领域，增强人们对基因和环境协同调节青春期发育的理解。

Abstract

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.

Sun Y, Fang J, Wan Y, Su P, Tao F. Role of polygenic risk in susceptibility to accelerated pubertal onset following chronic stress exposure. Eur J Endocrinol. 2019 Aug;181(2):129-137.