Polygenic interactions with adiposity rebound in the prediction of thelarche

The earliest onset of puberty had shifted downward, which may be due to the role of early growth and development factors in childhood.

All of 1575 Kindergarten Two (K2) children from Anhui province, China were followed up to elementary school. Girls (n = 342) with available data on AR and breast development were included for this analysis. Polygenic risk score (PRS) was computed based on 17 single nucleotide polymorphisms for early puberty. Accelerate failure time (AFT) model was used to describe thelarche timing by early AR among girls with different polygenic susceptibility.

After adjustment for perinatal anthropometric, household income, parental education and prepuberty BMI-Z score, puberty started 4.12-month earlier in early AR girls compared with normal AR girls (TR: 0.96; 95% CI: 0.95, 0.98, p < 0.001). Furthermore, this puberty-accelerating effect was observed among girls with high (6.06-month earlier, TR: 0.94; 95% CI: 0.90, 0.99) and moderate PRS (4.20-month earlier, TR: 0.96; 95% CI: 0.93, 0.98). No similar results were observed in the low PRS groups (TR: 1.00; 95% CI: 0.96, 1.04).

Girls with early AR displayed younger age at thelarche; however, this accelerating effect was only observed among those with genetic susceptibility to early puberty.

Early AR plays a more important role in predicting earlier thelarche among girls with high and moderate PRS. This study combined with the hot topics of pubertal-related polygenic risk score (PRS) for pubertal timing to examine the longitudinal association between early AR with accelerated pubertal onset. Our results mean that accelerating growth in the early childhood years after birth might forecast early puberty only among girls with genetic predisposition to early puberty. Prevention strategies and management options should be emphasized to target early childhood to address secular trend for early puberty observed in the past decades in China.