A large international study finds that the age at which girls reach puberty – marked by the timing of their first menstrual period – is decided by a small subset of genes they inherit from one parent. For the study, published in the journal Nature, scientists from 166 research centers worldwide analyzed data on over 180,000 women.
One of the investigating centers was the University of Cambridge in the UK.Senior author and pediatrician Dr. Ken Ong, of Cambridge’s Medical Research Council (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.”
Previous studies show that the timing of puberty in girls is a trait that is inherited, varies widely among individuals, and is linked to risks for obesity, type 2 diabetes, heart disease, breast cancer, and early death.
However, the underlying mechanisms that determine the timing of puberty, and how they link to disease, are not clear.
This study examines data from 57 studies that had analyzed the DNA of 182,416 women of European descent, and identifies 123 gene variants linked to timing of first menstrual cycle.
When a child is conceived, he or she has a new genome made of pairs of genes. Each pair of genes has one version from the biological mother and the other from the biological father.
The “usual” rule is that the two copies of a gene are expressed equally in the new individual. For example, if a child inherits a gene for blood group A from one parent, and the gene for blood group B from the other, the child’s blood group will be AB.
But there are subsets of genes, called “imprinted” genes, that do not follow these equal expression rules. In imprinted genes, only one version, either the one inherited from the mother, or the one inherited from the father, is expressed. The other gene is effectively silenced with a chemical tag.
SIX OF THE VARIANTS LINKED TO PUBERTY IN GIRLS ARE ‘IMPRINTED’ GENES
The researchers in this new study discovered that six of the 123 gene variants linked to timing of first menstrual cycle in girls are clustered within imprinted regions of the genome.
Lead author Dr. John Perry, Senior Investigator Scientist in the Cambridge MRC Epidemiology Unit says:
“Our findings imply that in a family, one parent may more profoundly affect puberty timing in their daughters than the other parent.”
The parent the gene comes from appears to determine the activity of imprinted genes. Some genes are only active if the mother’s copy is expressed, while others are only active if the father’s copy is expressed.
The study finds both types influence puberty timing in girls, suggesting a potential conflict between the parents’ genes over their child’s rate of development.
The researchers found more evidence to support the idea of imbalance between the father’s and the mother’s genes from analyzing data on another 35,000 women in Iceland.
This is the first study to show imprinted genes can influence development after birth:
“We knew that some imprinted genes control antenatal growth and development,” Dr. Perry explains, “but there is increasing interest in the possibility that imprinted genes may also control childhood maturation and later life outcomes, including disease risks.”
Dr. Ong says they will continue to study 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.”