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JOURNAL ARTICLE
REVIEW
Normal Variation in Pubertal Timing: Genetic Determinants in Relation to Growth and Adiposity.
In humans, there is a considerable variation in age of onset of puberty. Twin studies have indicated that pubertal timing is a highly heritable trait. Recently, a few rare genetic causes of precocious puberty have been reported as well as genetic mutations associated with isolated hypogonadotropic hypogonadism. Genome-wide association (GWA) studies have helped to explore the genetic determinants of the normal variation in pubertal timing, but have been able to explain only 2.7% of the variance in age at menarche, highlighting the involvement of multiple genes with small effect sizes. These studies indicate an overlap of genes involved in pubertal timing and adiposity, and epidemiological data suggest the existence of a pathway of early infancy weight gain, increased height gain in childhood, earlier pubertal timing and increased adiposity in adulthood. This chapter summarises the data from GWA and epidemiological studies on the normal variation in pubertal timing in relation to growth and adiposity. We discuss putative mechanisms linking early life events to pubertal timing, potential short-term and life-course consequences of earlier pubertal timing, and the impact of these data on clinical management of pubertal disorders.
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