The genetics of pubertal timing in the general population

Abstract

Purpose of review To overview advances in the genetics of puberty based on studies in the general population, describe evidence for sex-specific genetic effects on pubertal timing, and briefly review possible mechanisms mediating sexually dimorphic genetic effects. Recent findings 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 body mass index (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. While 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. Summary 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.

Association between factors related to the pregnancy, neonatal period, and later complications (especially asthma) and menarcheal age in a sample of Lebanese girls

“…However, our result was not affected by the BMI of the girls, in contradiction to the studies demonstrating that maternal age at menarche can only predict the age of the first menstruation in non-obese girls [ 22 ]. This proven relationship highlights the importance of the possible influence of genetic factors, which may determine the variation of the timing of menarche and puberty in girls in around 50–80% of the time [ 18 , 19 , 21 ]. The mean age of mothers’ menarche in our study was 12.44 years, delayed by 0.05 years than that of the girls, which can be explained by the trend toward an earlier puberty during these years, which stabilized recently [ 58 ].…”

“…In addition, genetics play a major role in controlling the timing of puberty, although only a very small percentage of these specific genes and trait variants is known so far [ 18 , 19 ]. This might explain the relationship found between the mothers’ precocious menarcheal age and the manifestation of a precocious thelarche and menarche in their daughters [ 20 , 21 ].…”

The Makorin lep-2 and the lncRNA lep-5 regulate lin-28 to schedule sexual maturation of the C. elegans nervous system

“…); and some phenotypes of heterochronic mutants can be considered sexual transformations (Ambros and Horvitz, 1984). Interestingly, many aspects of the timing of mammalian puberty also appear to be sex-specific (Abreu and Kaiser, 2016; Cousminer et al, 2016). Together, these observations blur the distinctions between sexual differentiation mechanisms and developmental timing pathways, helping provide a mechanistic understanding of the observation that sexual dimorphism often arises through heterochrony (McNamara, 2012).…”

Biological Aging in Childhood and Adolescence Following Experiences of Threat and Deprivation: A Systematic Review and Meta-Analysis

“…Given associations between threat-related adversity and altered diurnal patterns of cortisol and cortisol reactivity in childhood (Carpenter, Shattuck, Tyrka, Geracioti, & Price, 2011;Jaffee et al, 2014;King et al, 2017;Tyrka et al, 2009), it is plausible that trauma-related alterations of the HPA-axis may interact with the HPG-axis to accelerate the onset of pubertal development Saxbe et al, 2015). It is also important to consider the role of gene-environment correlation in the association between threat-related ELA and pubertal timing (Cousminer, Widén, & Palmert, 2015;Harden, 2014;Rowe, 2002). For instance, mothers who experience earlier onset of puberty may reproduce at an earlier age, and have children who are both more likely to experience trauma and an earlier onset of puberty (de Vries, Kauschansky, Shohat, & Phillip, 2004;Towne et al, 2005).…”