Genetics found to influence puberty timing in girls and boys

By looking at data on when boys’ voices first broke as a way to time the onset of puberty, researchers at Boys Choirthe University of Cambridge have completed a first-of-its-kind genetic study and found that for both boys and girls puberty is influenced by many of the same genetic variants.

“Our study shows that although there are obvious physical differences in pubertal development between boys and girls, many of the underlying biological processes governing it are the same,” said study lead author Dr. John Perry,   of the Medical Research Council (MRC) Epidemiology Unit at the University of Cambridge.

The study, published in Nature Communications, is the biggest large-scale genetic study of puberty to look at both young men and women together. Part of what is unique about this study is the novel way researchers determined the age of puberty in young men.

Using data from 55,000 male 23andMe customers who consented to research, the authors of the study used the participants recollection of their age when their voice first broke as a marker for puberty and found genetic variants associated with earlier onset of puberty in boys.

“(The study) also shows that the age when men’s voices break, even when recalled decades after the event, is an informative measure of puberty timing” co-author Dr. Felix Day, who is also at the MRC Epidemiology Unit at the University of Cambridge.

Up until now most of scientists understanding of the genetics of puberty came from studies that look at either rare disorders in young men, or studies that focused on young women alone. This novel way of looking at puberty in young men – asking men to recall the age they were at when their voices changed – allowed researchers to compare the genetic influence on the timing of puberty in both sexes.

What they found was surprising, more than a dozen genetic variants that influence the timing of puberty in women, also influence the timing of puberty in men. In addition, the researchers also found that some of those genetic variants are correlated with conditions developed later in life such Type II diabetes, cardiovascular disease, obesity and fasting insulin levels.

The researchers picked voice breaking to gauge the onset of male puberty because it is a distinct development milestone in young men that happens when their larynx lengthens due to exposure to more male hormone. After they looked at the genetic associations among men for onset of puberty, the researchers then compared that data to information from more than 180,000 women who were part of a consortium study, called ReproGen, as well as from the 1000 Genomes Project, and data on puberty from more than 76,000 women who are also 23andMe customers and consented to research. What they found was that of the 14 genetic variants found to be associated with puberty, five had never before been associated with puberty.

The nine other variants had been previously identified as associated with the timing of puberty in young women, but this was the first time any researchers found an association for the timing of puberty in young men. This study is the first to quantify the strongly shared genetic basis for puberty timing between the sexes, and, according to the researchers, the results are consistent with previous studies that looked at sex-specific rare disorders of puberty.

The study also offers additional insight into the biological pathways and process of early puberty, by looking at the function of the genes and gene regions where these variants are located. For example, two of the newly found variants are located in or near the genes RORB and RXRA, which regulate cell differentiation, cell development, circadian rhythm and metabolism.

“Other studies have shown that earlier age at puberty in girls predicts higher risks for the same diseases. We now show that the same is true in men,” said Dr. Ken Ong, of the MRC Epidemiology Unit and a co-author of the study. “The next steps will be to understand how to prevent early puberty in boys and girls, possibly by reducing childhood overweight and obesity, or by other means.”

But he added that while many of those correlations with earlier puberty were for adverse conditions, earlier puberty was correlated with at least one favorable condition – higher bone mineral density.