Background: Menarche is the first menstrual period of a girl at puberty. The timing of menarche is important for health in later life. Age at menarche is a complex trait and has a strong genetic component. This review summarizes the results of the genetic studies of age at menarche conducted to date, highlights existing problems in this area and outlines prospects of future studies on genetic factors for the trait.
Methods: PubMed and Google Scholar were searched until May 2011 using the keywords: 'menarche', 'puberty' and 'age at menarche' in combination with the keywords 'polymorphism', 'candidate gene', 'genome-wide association study' and 'linkage'.
Results: Our search yielded 170 papers, 35 of which were selected for further analysis. Several large-scale genome-wide association studies along with a powerful meta-analysis of their aggregated data identified about 50 candidate genes for the trait. Some genes were replicated in different studies of Caucasians (e.g. LIN28B, TMEM38B) or in different ethnicities (e.g. SPOCK, RANK and RANKL). However, despite the large volume of results obtained, there is a huge gap in relevant data on ethnic groups other than Caucasians.
Conclusions: The reviewed studies laid a solid basis for future research on genetics of age at menarche. However, as yet specific genes for this trait have not been identified consistently in all ethnicities and types of studies. We suggest expanding the research to different ethnicities and propose several methodologies to increase the efficiency of studies in this area, including a systems approach, which combines existing high-throughput methods in a single pipeline.