Study of age of puberty in girls suggests links with weight gain

Genes may indirectly influence how old girls are when they have their first period by speeding up weight gain in childhood – a known risk factor for early puberty, researchers have found.

Other genes can directly affect the age of puberty, according to the study.

Being able to predict who is at high risk of early puberty could enable families and doctors to take action in order to reduce this risk, which is associated with increased risk of a number of diseases in later life, including type 2 diabetes, and heart disease.

Later puberty has been linked to improved health in adulthood and living longer.

In the largest study of its kind to date, an international team led by researchers at the Medical Research Council (MRC) Epidemiology Unit, University of Cambridge, studied the DNA of around 800,000 women from Europe, North America, China, Japan, and Korea.

They found more than 1,000 variants – small changes in DNA – that influence the age of the first period.

Around 600 of these variants were observed for the first time.

Corresponding author Professor John Perry said: “Many of the genes we’ve found influence early puberty by first accelerating weight gain in infants and young children.

“This can then lead to potentially serious health problems in later life, as having earlier puberty leads to higher rates of overweight and obesity in adulthood.”

Cambridge’s Professor Ken Ong, one of the researchers involved in the study, said the links with higher risks of serious disease later in life highlight the public health importance of avoiding earlier puberty timing.

He added: “For individual children and families, a more immediate impact of earlier puberty may be more risk-taking behaviour by associating with older youth and negative impacts on school performance.

“Prediction of young children at high risk of early puberty might enable lifestyle, behavioural or simple medical approaches to reduce this risk.”

In girls, puberty and periods normally start between the ages of 10 to 15, but experts say this has been getting earlier and earlier in recent decades.

Just under half (45%) of the genetic variants discovered in the study affected puberty indirectly, by increasing weight gain in early childhood, the researchers say.

Previous research has shown that a receptor in the brain detects the nutritional state of the body and regulates the timing of puberty and rate of growth in children.

Dr Katherine Kentistou, lead study investigator, said: “This is the first time we’ve ever been able to analyse rare genetic variants at this scale.

“We have identified six genes which all profoundly affect the timing of puberty.

“While these genes were discovered in girls, they often have the same impact on the timing of puberty in boys.

“The new mechanisms we describe could form the basis of interventions for individuals at risk of early puberty and obesity.”

In the new study, the researchers also created a genetic score that predicted whether a girl was likely to hit puberty very early or very late.

Girls with the highest 1% of this genetic score were 11 times more likely to have extremely delayed puberty – after 15-years-old.

On the other hand, girls with the lowest 1% genetic score were 14 times more likely to have extremely early puberty – before the age of 10.

Senior author and paediatrician Prof Ong said: “In the future, we may be able to use these genetic scores in the clinic to identify those girls whose puberty will come very early or very late.

“The NHS is already trialling whole genome sequencing at birth, and this would give us the genetic information we need to make this possible.”

The findings are published in the Nature Genetics journal.