Biggest genetic study on girls’ puberty age links it to weight gain

Studying genetic complexity in puberty timing.

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A University of Cambridge-led study found that genes can speed up weight gain in childhood, leading to early puberty. Some genes directly affect puberty timing. Researchers studied DNA from 800,000 women and found over 1,000 genetic variants influencing the age of the first period.

Girls typically hit puberty and start having periods between ages 10 and 15, but this has been happening earlier in recent decades for unknown reasons. Early puberty is linked to higher risks of diseases like type 2 diabetes, heart disease, and certain cancers. Later puberty is associated with better health and longer life.

About 45% of the genetic variants found affect puberty by increasing early childhood weight gain. Professor John Perry explained that many genes cause early puberty by speeding up weight gain in infants, leading to serious health issues later in life.

Previous research by the team found that a brain receptor, MC3R, senses the body’s nutrition and controls puberty timing and growth in children. Other genes in the brain control reproductive hormone release.

The scientists also studied rare genetic variants affecting puberty. They found that one in 3,800 women with a variant in the gene ZNF483 experienced puberty 1.3 years later on average.

Dr. Katherine Kentistou said, “This is the first large-scale analysis of rare genetic variants, identifying six genes significantly impacting puberty timing. These findings could help develop interventions for early puberty and obesity.”

Researchers created a genetic score to predict when girls will hit puberty. Girls with the highest 1% score were 11 times more likely to have very late puberty (after age 15), while those with the lowest 1% score were 14 times more likely to have very early puberty (before age 10).

Professor Ken Ong said that in the future, these genetic scores could help identify girls at risk for early or late puberty. The NHS is already testing whole genome sequencing at birth, which could provide the necessary genetic information.

Currently, children with very early puberty (age 7 or 8) are offered puberty blockers, but more interventions are needed for those who miss this threshold. This could be crucial for their future health.

Journal reference:

  1. Kentistou, K.A., Kaisinger, L.R., Stankovic, S. et al. Understanding the genetic complexity of puberty timing across the allele frequency spectrum. Nature Genetics. DOI: 10.1038/s41588-024-01798-4.

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