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CAMBRIDGE, United Kingdom — One of the telltale signs of puberty in girls is their first menstrual cycle. While it usually occurs between the ages of 10 and 15, the age of puberty has been starting earlier in recent decades. Starting puberty early is a growing concern among doctors because it is often linked to an increased risk of Type 2 diabetes, heart disease, and certain cancers later on in life. Meanwhile, starting puberty later is associated with better health and a longer lifespan.
The factors that determine when a girl would start puberty — and why it’s happening at an earlier age recently — have been unknown until now. However, a study published in Nature Genetics has identified over 1,000 small changes in DNA that influence the timing of a girl’s first period — including many with a strong connection to weight gain.
“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,” says John Perry, a professor at the University of Cambridge and co-author of the study, in a media release.
This is the largest genetic study analyzing the age of puberty with DNA samples collected from all over the world, including Europe, North America, Japan, South Korea, and China.
Methodology
The research team analyzed genetic information from over 800,000 women worldwide. Their focus was on finding genetic variants that, while only carried by a portion of the population, have a major impact on puberty.
For example, prior research by the team found a brain receptor called MC3R that is involved in detecting how the body is doing nutritionally and also regulates growth rate and puberty timing. Other genes have been shown to control the release of reproductive hormones in the brain.
Besides looking for rare genetic variants, the authors created a genetic score to predict when a girl would hit puberty very early or very late.
“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,” says Dr. Katherine Kentistou, the lead study author.
Results
Over 1,000 genetic variations related to puberty were identified in women, and about 600 of these genetic variants have been observed for the very first time. Six rare genetic changes in girls were found to influence the timing of puberty. For example, 3,800 women carried a rare change to the ZNF483 gene, which caused women to start puberty 1.3 years later. Additionally, 45% of the discovered genes indirectly influenced puberty by accelerating childhood weight gain.
When tallying up a girl’s genetic score, those in the highest 1% in terms of their scores were 11 times more likely to experience extremely delayed puberty (after age 15). Girls with the lowest 1% of genetic scores were 14 times more likely to get their period extremely early (before age 10).
Discussion & Takeaways
The goal is to ensure girls do not go through puberty too early in life. According to the authors, collecting genetic information and calculating genetic scores will help doctors identify those at high risk for early puberty and allow enough time to delay it via puberty blockers.
“This is the first time we’ve ever been able to analyze rare genetic variants at this scale. We have identified six genes which all profoundly affect the timing of puberty,” says Dr. Kentistou. “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.”
