The Polygenic and Monogenic Basis of Paediatric Fractures

S. Ghatan, A. Costantini, R. Li, C. De Bruin, N. M. Appelman-Dijkstra, E. M. Winter, L. Oei, Carolina Medina-Gomez*

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

2 Citations (Scopus)
46 Downloads (Pure)


Purpose of Review: Fractures are frequently encountered in paediatric practice. Although recurrent fractures in children usually unveil a monogenic syndrome, paediatric fracture risk could be shaped by the individual genetic background influencing the acquisition of bone mineral density, and therefore, the skeletal fragility as shown in adults. Here, we examine paediatric fractures from the perspective of monogenic and complex trait genetics. Recent Findings: Large-scale genome-wide studies in children have identified ~44 genetic loci associated with fracture or bone traits whereas ~35 monogenic diseases characterized by paediatric fractures have been described. Summary: Genetic variation can predispose to paediatric fractures through monogenic risk variants with a large effect and polygenic risk involving many variants of small effects. Studying genetic factors influencing peak bone attainment might help in identifying individuals at higher risk of developing early-onset osteoporosis and discovering drug targets to be used as bone restorative pharmacotherapies to prevent, or even reverse, bone loss later in life.

Original languageEnglish
Pages (from-to)481-493
Number of pages13
JournalCurrent Osteoporosis Reports
Issue number5
Early online date4 May 2021
Publication statusPublished - Oct 2021

Bibliographical note

Funding Information:
This work has been financially supported by the Netherlands Organization for Health Research and Development (ZonMw VIDI 016.136.367). S. G. and R. L. are supported by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 860898. A. C. is financially supported by the International Postdoc Grant from the Swedish Research Council (2020-00587). L. O. is funded by an Erasmus MC fellowship grant.

Publisher Copyright:
© 2021, The Author(s).


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