A massive genetic study involving 800,000 women has uncovered new insights into the timing of puberty in girls. The research, led by Cambridge University scientists, found over 1,000 genetic variants that influence when girls start menstruating, with many linked to childhood weight gain.
The age girls begin menstruating has been decreasing in recent decades, a trend associated with increased health risks later in life. This new study, published in Nature Genetics, sheds light on the complex interplay between genes, weight, and puberty timing.
Weight Gain: A Key Factor in Early Puberty
Nearly half of the genetic variants discovered in the study affect puberty indirectly by increasing weight gain in early childhood. This finding highlights the crucial role of body weight in determining when girls enter puberty.
Professor John Perry, corresponding author of the study, explained: “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.”
Previous research by the team identified a brain receptor called MC3R that detects the body’s nutritional state and regulates puberty timing and growth rate in children. Other genes found in the current study appear to control the release of reproductive hormones in the brain.
Rare Variants with Profound Effects
The researchers also analyzed rare genetic variants carried by very few individuals but with significant impacts on puberty timing. For instance, they found that one in 3,800 women carry variants in the ZNF483 gene, causing them to experience puberty an average of 1.3 years later than normal.
Dr. Katherine Kentistou, lead study investigator, noted: “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 team developed a genetic score to predict whether a girl is likely to experience very early or very late puberty. Girls with the highest 1% of this genetic score were 11 times more likely to have extremely delayed puberty (after age 15), while those with the lowest 1% were 14 times more likely to have extremely early puberty (before age 10).
Senior author and pediatrician Professor Ken Ong highlighted the potential clinical applications: “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.”
This groundbreaking research, supported by the Medical Research Council and including data from the UK Biobank, opens new avenues for understanding and potentially intervening in puberty timing. As early puberty is linked to increased health risks, these findings could have significant implications for public health strategies and personalized medicine approaches in the future.
