The study looks at the genes that control when puberty starts, especially MKRN3, DLK1, and the kisspeptin system (KISS1/KISS1R). It shows that loss‑of‑function mutations in MKRN3 are the most common genetic cause of early puberty, that DLK1 mutations can also trigger it, and that rare KISS1/KISS1R changes are linked to the same condition. This information is mostly about childhood development and isn’t directly useful for adult health hacks.

Pubertal timing is regulated by the complex interplay of genetic, environmental, nutritional and epigenetic factors. Criteria for determining normal pubertal timing, and thus the definition of precocious puberty, have evolved based on published population studies. The significance of the genetic influence on pubertal timing is supported by familial pubertal timing and twin studies. In contrast to the many monogenic causes associated with hypogonadotropic hypogonadism, only four monogenic causes of central precocious puberty (CPP) have been described. Loss-of-function mutations in Makorin Ring Finger Protein 3(MKRN3), a maternally imprinted gene on chromosome 15 within the Prader-Willi syndrome locus, are the most common identified genetic cause of CPP. More recently, several mutations in a second maternally imprinted gene, Delta-like noncanonical Notch ligand 1 (DLK1), have also been associated with CPP. Polymorphisms in both genes have also been associated with the age of menarche in genome-wide association studies. Mutations in the genes encoding kisspeptin (KISS1) and its receptor (KISS1R), potent activators of GnRH secretion, have also been described in association with CPP, but remain rare monogenic causes. CPP has both short- and long-term health implications for children, highlighting the importance of understanding the mechanisms contributing to early puberty. Additionally, given the role of mutations in the imprinted genes MKRN3 and DLK1 in pubertal timing, other imprinted candidate genes should be considered for a role in puberty initiation.