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Largest ever genetic study of age of puberty in girls shows links with weight gain

Genes can indirectly influence the age at which girls have their first period by accelerating weight gain in childhood, a known risk factor for early puberty, a study from the University of Bergen and University of Cambridge has found. Other genes can directly affect age of puberty, some with profound effects.

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The age at which girls hit puberty and start having periods normally occurs between ages 10 to 15, though this has been getting earlier and earlier in recent decades. The reasons for this are not fully understood.

The largest genetic study of its kind

In the largest study of its kind to date, an international team studied the DNA of around 800,000 women from Europe, North America, China, Japan, and Korea. Published this week in Nature Genetics, the researchers found more than 1,000 variants – small changes in DNA – that influence the age of first menstrual period.

Researchers from the University of Bergen contributed with analyses of 27 000 participants from the Norwegian Mother, father and child birth-cohort (MoBa). Professsor Stefan Johansson from the medical faculty at UiB and leader of the Norwegian part of the study said

“We analysed how these identified DNA variants influenced weight development during early childhood in the Norwegian MoBa participants, and we could show that just under half (45%) of the discovered genetic variants affected puberty indirectly, by increasing weight gain in early childhood.”

“Previous work from the Cambridge team has shown that a receptor in the brain, known as MC3R, detects the nutritional state of the body and regulates the timing of puberty and rate of growth in children, providing a mechanism by which this occurs. Other identified genes appeared to be acting in the brain to control the release of reproductive hormones. In the new study we also used new DNA sequencing methods that allowed us for the first time to analyse rare genetic variants at scale. We identified several genes which all profoundly affect the timing of puberty.”

Also boys are affected

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.” Concludes professor at UiB Marc Vaudel, who performed the genetic analyses in the MoBa cohort.