Gene variants influence onset of menstruation

The first evidence for a genetic influence on the timing of female sexual maturation has been found by an international team of scientists, led by the Institute of Biomedical and Clinical Science in the Peninsula Medical School at Exeter (PMSE). The study, reported in the journal Nature Genetics, showed that women with two copies of particular gene variants start menstruating on average about four and a half months earlier than those without any copies. A second, related study published in the same journal and led by the MRC Epidemiology Unit at Cambridge (MREUC) shows that the gene variants are located close to others that influence height and weight, for both girls and boys.

The findings may help to explain why some girls begin puberty especially early, and also why relatively shorter girls with higher body mass indexes (BMIs) often reach menarche (first menstruation) before their peers. The discovery is an important step forward in scientists' understanding of the processes that govern the reproductive lifespan. It will also shed new light on women's risks of developing conditions that are closely linked to early puberty and a longer exposure to reproductive hormones over their lives, such as diabetes, osteoporosis, heart disease and breast cancer.

Genetic data from over 17,500 women who had reached menarche between the ages of nine and 17 years - collated and analysed from previous studies across eight different international population-based sources - was analysed by the Exeter-led team. They predict that one in 20 women carries two copies of the gene variants near the LIN28B gene, which lead to earlier menarche.

The Cambridge-led team linked other variants in this same gene to early breast development in girls, and early voice breaking and pubic hair development in boys. The fact that the variants affect both males and females points to a more general role of LIN28B in puberty and the timing of growth.

Lead researcher of the Cambridge-led team, Dr Ken Ong explains that 'LIN28B works by controlling whether or not other genes are active'. The LIN28B gene might therefore act as a sort of 'master switch' for adolescent development, but, as Dr Ong points out, 'this is the first evidence linking such a gene to growth and physical maturation'.

However, the effect of a single gene is likely to be relatively small; the onset of puberty is also influenced by factors such as nutrition and exercise. Girls usually begin menstruation between the ages of nine and 16, and the variations found in LIN28B accounted for just one to three months of this variation. Three other papers, also published in Nature Genetics, offer other candidate genes which may also be involved in the onset of puberty. As André Uitterlinden, a geneticist at Erasmus Medical Center (EMC) in Rotterdam, the Netherlands, explains 'it's sort of the tip of the iceberg'.