Puberty comes earlier –

MADRID (EFE).— Genes can indirectly influence the age at which girls have their first period by accelerating weight gain in childhood, a known risk factor for precocious puberty, according to the largest genetic study to date.

The work also found that other genes can directly affect the age of puberty, some with profound effects that affect adulthood.

These are some of the findings of the largest genetic study of female puberty in history, an international study led by the University of Cambridge based on the analysis of the DNA of some 800,000 women from Europe, North America, China, Japan and Korea.

According to Nature Genetics, researchers found more than a thousand variants—small changes in DNA—that influence the age of first menstruation, and nearly 600 of these variants were previously unknown.

The age at which girls reach puberty and start having periods ranges from 10 to 15 years, but in recent decades this has been happening earlier and earlier, although the reasons are not fully understood.

Precocious puberty is linked to an increased risk of a number of diseases later in life, including type 2 diabetes, cardiovascular disease and certain types of cancer.

In contrast, later puberty has been linked to better health in adulthood and greater longevity. Just under half (45%) of the genetic variants discovered indirectly affected puberty, through weight gain in early childhood.

Consequences

“Many of the genes we found influence precocious puberty by first accelerating weight gain in babies and young children. This can lead to serious health problems later in life, as precocious puberty leads to higher rates of overweight and obesity in adulthood,” warns John Perry, lead author of the study.

Previous work by the team showed that a receptor in the brain, known as MC3R, senses the nutritional status of the body and regulates the timing of puberty and the rate of growth in children, providing a mechanism by which this occurs. Other genes identified appeared to act in the brain to control the release of reproductive hormones.

The scientists also looked at rare genetic variants that very few people have, but which can have big effects on puberty. For example, they found that one in 3,800 women has mutations in the gene ZNF483, which caused them to start puberty an average of 1.3 years later.

“We have identified six genes that profoundly affect the timing of puberty. And although 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 precocious puberty and obesity,” explains the study’s lead researcher, Katherine Kentistou.

The researchers also generated a genetic score that predicted whether a girl was likely to hit puberty too early or too late.

Girls with the highest 1% of this genetic score were eleven times more likely to have extremely late puberty, i.e. after age 15.

On the other hand, girls with the lowest 1% genetic score were fourteen times more likely to have extremely precocious puberty, that is, before the age of 10.

For Ken Ong, senior author and paediatrician, “In future, we may be able to use these genetic scores in the clinic to identify girls who will have very early or very late puberty. The NHS is already trialling whole genome sequencing at birth, which would give us the genetic information needed to make this possible.”

“Children who present to the NHS with very precocious puberty – at seven or eight years old – are offered puberty blockers to delay it. But the age of puberty is a continuum, and if they don’t reach this threshold, we have nothing to offer them. We need other interventions to help, whether it’s oral medication or a behavioural approach, because this could be important for their health when they get older.”