Certain genes linked to early puberty in girls

A girl's genetics can indirectly influence the age when she has her first period, by accelerating her weight gain in childhood, a new study finds.

A number of other genes also can directly affect the age of puberty, some with profound effects, researchers added.

More than 1,000 genetic variants are tied to the age of a girl's first menstrual period, researchers discovered by analyzing the genes of about 800,000 women. About 600 of these variants were observed for the first time in this study.

A girl can have up to 14-fold higher risk of early puberty if her genetics line up that way, according to a genetic risk score researchers created from their findings.

"This is the first time we've ever been able to analyze rare genetic variants at this scale," said lead researcher Katherine Kentistou , a senior research associate with the University of Cambridge's Medical Research Council Epidemiology Unit.

"We have identified six genes which all profoundly affect the timing of puberty," she said in a news release. "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."

Girls typically enter puberty typically between 10 and 15 years of age, but this has been getting earlier and earlier in recent decades.

Early puberty is linked with increased risk for many diseases later in life, including type 2 diabetes, heart disease and certain cancers, researchers said in background notes. On the other hand, later puberty has been linked to better adult health and longer lifespan.

In the study, researchers found that 45% of the gene variants that affect puberty do so indirectly by increasing weight gain in youngsters.

"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," researcher John Perry , an investigator with the University of Cambridge Medical Research Council Epidemiology Unit, said in a news release.

The team also analyzed rare genetic variants that can have a large effect on puberty.

For example, a variant in the gene ZNF483 can cause women to experience puberty an average 1.3 years later. About 1 in 3,800 women carry this variant, researchers said.

The team also created a genetic score that could predict 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 reach puberty after age 15, which researchers described as extremely delayed.

Likewise, girls with the lowest 1% genetic score were 14 times more likely to have extremely early puberty before age 10.

"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," senior researcher Ken Ong , an investigator with the University of Cambridge Medical Research Council Epidemiology Unit, said in a news release.

Girls who present with very early puberty can be offered puberty blockers to delay its onset, he said.

"But age of puberty is a continuum, and if they miss this threshold, there's currently nothing we have to offer," Ong said. "We need other interventions, whether that's oral medication or a behavioral approach, to help. This could be important for their health when they grow up."

The new study was published Monday in the journal Nature Genetics .

More information

Boston Children's Hospital has more about precocious puberty .

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