Genetics of Age at Menarche

Abstract

Age at menarche, defined as the age at first menstruation, is a complex trait influenced by both environmental and genetic factors. A younger age at menarche has been linked to increased risks later in life for a number of diseases including reproductive cancers, cardiovascular and metabolic disorders and osteoporosis. A better understanding of the genetic factors influencing menarche may not only help us to gain more mechanistic insight into normal reproduction functions and those associated diseases, but may also have important clinical implications for the identification of high‐risk subgroups that may benefit from early intervention. Our current knowledge of the genetic basis of age at menarche mainly comes from the results from linkage analysis, and candidate gene and genome‐wide association studies. New technologies and approaches, such as next‐generation sequencing and integrative molecular epidemiology, may provide useful tools for the further discovery of the genetic factors impacting age at menarche. Key Concepts: Age at menarche varies substantially between individuals. A younger age at menarche has been linked to increased risks for cancer, cardiovascular, and metabolic disorders. Age at menarche is a complex trait that is influenced by both environmental and genetic factors. It is estimated that approximately 50% of the observed variation in age at menarche is contributed by genetic factors. Different genetic approaches have identified genetic loci that are responsible for age at menarche. However, the confirmed genetic loci can only explain a small proportion of the observed variation. Future studies of the genetics of age at menarche will focus on rare genetic variations, gene–environment interactions and functional characterisation of the identified genetic variations. Identification of the genetic factors impacting age at menarche may help us to understand normal reproduction functions and diseases associated with menarche timing. This information may then be translated into clinical applications that might allow us to predict early menarche and to identify high‐risk subgroups that might benefit from early interventions.