The findings come from an international study of more than 180,000 women involving scientists from 166 institutions worldwide, including the University of Cambridge. The researchers identified 123 genetic variations that were associated with the timing of when girls experienced their first menstrual cycle by analysing the DNA of 182,416 women of European descent from 57 studies. Six of these variants were found to be clustered within imprinted regions of the genome.



Lead author Dr John Perry at the Medical Research Council (MRC) Epidemiology Unit, University of Cambridge says: “Normally, our inherited physical characteristics reflect a roughly average combination of our parents’ genomes, but imprinted genes place unequal weight on the influence of either the mother’s or the father’s genes. Our findings imply that in a family, one parent may more profoundly affect puberty timing in their daughters than the other parent.”



The activity of imprinted genes differs depending on which parent the gene is inherited from – some genes are only active when inherited from the mother, others are only active when inherited from the father. Both types of imprinted genes were identified as determining puberty timing in girls, indicating a possible biological conflict between the parents over their child’s rate of development. Further evidence for the parental imbalance in inheritance patterns was obtained by analysing the association between these imprinted genes and timing of puberty in a study of over 35,000 women in Iceland, for whom detailed information on their family trees were available.



This is the first time that it has been shown that imprinted genes can control rate of development after birth.



Dr Perry says: “We knew that some imprinted genes control antenatal growth and development – but there is increasing interest in the possibility that imprinted genes may also control childhood maturation and later life outcomes, including disease risks.”



Senior author and paediatrician Dr Ken Ong at the MRC Epidemiology Unit says: “There is a remarkably wide diversity in puberty timing – some girls start at age 8 and others at 13. While lifestyle factors such as nutrition and physical activity do play a role, our findings reveal a wide and complex network of genetic factors. We are studying these factors to understand how early puberty in girls is linked to higher risks of developing diabetes, heart disease and breast cancer in later life – and to hopefully one day break this link.”



Dr Anna Murray, a co-author from the University of Exeter Medical School, adds: “We found that there are hundreds of genes involved in puberty timing, including 29 involved in the production and functioning of hormones, which has increased our knowledge of the biological processes that are involved, in both girls and boys.”



The study was supported in the UK by the Medical Research Council and the Wellcome Trust.