The genetics of pubertal timing in the general population: recent advances and evidence for sex-specificity

This article overviews advances in the genetics of puberty based on studies in the general population, describes evidence for sex-specific genetic effects on pubertal timing, and briefly reviews possible mechanisms mediating sexually dimorphic genetic effects. Pubertal timing is highly polygenic, and many loci are conserved among ethnicities. A number of identified loci underlie both pubertal timing and related traits such as height and BMI. It is increasingly apparent that understanding the factors modulating the onset of puberty is important because the timing of this developmental stage is associated with a wider range of adult health outcomes than previously appreciated. Although most of the genetic effects underlying the timing of puberty are common between boys and girls, some effects show sex-specificity and many are epigenetically modulated. Several potential mechanisms, including hormone-independent ones, may be responsible for observed sex differences. Studies of pubertal timing in the general population have provided new knowledge about the genetic architecture of this complex trait. Increasing attention paid to sex-specific effects may provide key insights into the sexual dimorphism in pubertal timing and even into the associations between puberty and adult health risks by identifying common underlying biological pathways.