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

Date:
July 1, 2024
Source:
University of Cambridge
Summary:
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. Other genes can directly affect age of puberty, some with profound effects.
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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 Cambridge-led study has found. Other genes can directly affect age of puberty, some with profound effects.

In the largest study of its kind to date, an international team led by researchers at the Medical Research Council (MRC) Epidemiology Unit, University of Cambridge, studied the DNA of around 800,000 women from Europe, North America, China, Japan, and Korea.

Published today in Nature Genetics, the researchers found more than 1,000 variants -- small changes in DNA -- that influence the age of first menstrual period. Around 600 of these variants were observed for the first time.

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. Early puberty is linked with increased risk of a number of diseases in later life, including type 2 diabetes, cardiovascular disease, and certain cancers. Later puberty on the other hand, has been linked to improved health in adulthood and a longer lifespan.

Just under half (45%) of the discovered genetic variants affected puberty indirectly, by increasing weight gain in early childhood.

Corresponding author Professor John Perry said: "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 work by the team -- together with researchers at Cambridge's MRC Metabolic Diseases Unit -- showed 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.

The scientists also analysed rare genetic variants that are carried by very few people, but which can have large effects on puberty. For example, they found that one in 3,800 women carry variants in the gene ZNF483, which caused these women to experience puberty on average, 1.3 years later.

Dr Katherine Kentistou, lead study investigator, added: "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 new mechanisms we describe could form the basis of interventions for individuals at risk of early puberty and obesity."

The researchers also generated a genetic score that predicted whether a girl was likely to hit puberty very early or very late. Girls with the highest 1% of this genetic score were 11 times more likely to have extremely delayed puberty -- that is, after age 15 years. On the other hand, girls with the lowest 1% genetic score were 14 times more likely to have extremely early puberty -- before age 10.

Senior author and paediatrician Professor Ken Ong said: "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.

"Children who present in the NHS with very early puberty -- at age seven or eight -- are offered puberty blockers to delay it. But age of puberty is a continuum, and if they miss this threshold, there's currently nothing we have to offer. We need other interventions, whether that's oral medication or a behavioural approach, to help. This could be important for their health when they grow up."

The research was supported by the Medical Research Council and included data from the UK Biobank.


Story Source:

Materials provided by University of Cambridge. The original text of this story is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Note: Content may be edited for style and length.


Journal Reference:

  1. Katherine A. Kentistou, Lena R. Kaisinger, Stasa Stankovic, Marc Vaudel, Edson Mendes de Oliveira, Andrea Messina, Robin G. Walters, Xiaoxi Liu, Alexander S. Busch, Hannes Helgason, Deborah J. Thompson, Federico Santoni, Konstantin M. Petricek, Yassine Zouaghi, Isabel Huang-Doran, Daniel F. Gudbjartsson, Eirik Bratland, Kuang Lin, Eugene J. Gardner, Yajie Zhao, Raina Y. Jia, Chikashi Terao, Marjorie J. Riggan, Manjeet K. Bolla, Mojgan Yazdanpanah, Nahid Yazdanpanah, Jonathan P. Bradfield, Linda Broer, Archie Campbell, Daniel I. Chasman, Diana L. Cousminer, Nora Franceschini, Lude H. Franke, Giorgia Girotto, Chunyan He, Marjo-Riitta Järvelin, Peter K. Joshi, Yoichiro Kamatani, Robert Karlsson, Jian’an Luan, Kathryn L. Lunetta, Reedik Mägi, Massimo Mangino, Sarah E. Medland, Christa Meisinger, Raymond Noordam, Teresa Nutile, Maria Pina Concas, Ozren Polašek, Eleonora Porcu, Susan M. Ring, Cinzia Sala, Albert V. Smith, Toshiko Tanaka, Peter J. van der Most, Veronique Vitart, Carol A. Wang, Gonneke Willemsen, Marek Zygmunt, Thomas U. Ahearn, Irene L. Andrulis, Hoda Anton-Culver, Antonis C. Antoniou, Paul L. Auer, Catriona L. K. Barnes, Matthias W. Beckmann, Amy Berrington de Gonzalez, Natalia V. Bogdanova, Stig E. Bojesen, Hermann Brenner, Julie E. Buring, Federico Canzian, Jenny Chang-Claude, Fergus J. Couch, Angela Cox, Laura Crisponi, Kamila Czene, Mary B. Daly, Ellen W. Demerath, Joe Dennis, Peter Devilee, Immaculata De Vivo, Thilo Dörk, Alison M. Dunning, Miriam Dwek, Johan G. Eriksson, Peter A. Fasching, Lindsay Fernandez-Rhodes, Liana Ferreli, Olivia Fletcher, Manuela Gago-Dominguez, Montserrat García-Closas, José A. García-Sáenz, Anna González-Neira, Harald Grallert, Pascal Guénel, Christopher A. Haiman, Per Hall, Ute Hamann, Hakon Hakonarson, Roger J. Hart, Martha Hickey, Maartje J. Hooning, Reiner Hoppe, John L. Hopper, Jouke-Jan Hottenga, Frank B. Hu, Hanna Huebner, David J. Hunter, Helena Jernström, Esther M. John, David Karasik, Elza K. Khusnutdinova, Vessela N. Kristensen, James V. Lacey, Diether Lambrechts, Lenore J. Launer, Penelope A. Lind, Annika Lindblom, Patrik K. E. Magnusson, Arto Mannermaa, Mark I. McCarthy, Thomas Meitinger, Cristina Menni, Kyriaki Michailidou, Iona Y. Millwood, Roger L. Milne, Grant W. Montgomery, Heli Nevanlinna, Ilja M. Nolte, Dale R. Nyholt, Nadia Obi, Katie M. O’Brien, Kenneth Offit, Albertine J. Oldehinkel, Sisse R. Ostrowski, Aarno Palotie, Ole B. Pedersen, Annette Peters, Giulia Pianigiani, Dijana Plaseska-Karanfilska, Anneli Pouta, Alfred Pozarickij, Paolo Radice, Gad Rennert, Frits R. Rosendaal, Daniela Ruggiero, Emmanouil Saloustros, Dale P. Sandler, Sabine Schipf, Carsten O. Schmidt, Marjanka K. Schmidt, Kerrin Small, Beatrice Spedicati, Meir Stampfer, Jennifer Stone, Rulla M. Tamimi, Lauren R. Teras, Emmi Tikkanen, Constance Turman, Celine M. Vachon, Qin Wang, Robert Winqvist, Alicja Wolk, Babette S. Zemel, Wei Zheng, Ko W. van Dijk, Behrooz Z. Alizadeh, Stefania Bandinelli, Eric Boerwinkle, Dorret I. Boomsma, Marina Ciullo, Georgia Chenevix-Trench, Francesco Cucca, Tõnu Esko, Christian Gieger, Struan F. A. Grant, Vilmundur Gudnason, Caroline Hayward, Ivana Kolčić, Peter Kraft, Deborah A. Lawlor, Nicholas G. Martin, Ellen A. Nøhr, Nancy L. Pedersen, Craig E. Pennell, Paul M. Ridker, Antonietta Robino, Harold Snieder, Ulla Sovio, Tim D. Spector, Doris Stöckl, Cathie Sudlow, Nic J. Timpson, Daniela Toniolo, André Uitterlinden, Sheila Ulivi, Henry Völzke, Nicholas J. Wareham, Elisabeth Widen, James F. Wilson, Esther M. John, Per Hall, Robert Winqvis, Paul D. P. Pharoah, Liming Li, Douglas F. Easton, Pål R. Njølstad, Patrick Sulem, Joanne M. Murabito, Anna Murray, Despoina Manousaki, Anders Juul, Christian Erikstrup, Kari Stefansson, Momoko Horikoshi, Zhengming Chen, I. Sadaf Farooqi, Nelly Pitteloud, Stefan Johansson, Felix R. Day, John R. B. Perry, Ken K. Ong. Understanding the genetic complexity of puberty timing across the allele frequency spectrum. Nature Genetics, 2024; DOI: No DOI!

Cite This Page:

University of Cambridge. "Largest ever genetic study of age of puberty in girls shows links with weight gain." ScienceDaily. ScienceDaily, 1 July 2024. <www.sciencedaily.com/releases/2024/07/240701131723.htm>.
University of Cambridge. (2024, July 1). Largest ever genetic study of age of puberty in girls shows links with weight gain. ScienceDaily. Retrieved July 17, 2024 from www.sciencedaily.com/releases/2024/07/240701131723.htm
University of Cambridge. "Largest ever genetic study of age of puberty in girls shows links with weight gain." ScienceDaily. www.sciencedaily.com/releases/2024/07/240701131723.htm (accessed July 17, 2024).

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