The Polygenic and Monogenic Basis of Paediatric Fractures

• Published in: Current osteoporosis reports Vol. 19; no. 5; pp. 481 - 493
• Main Authors: Ghatan, S., Costantini, A., Li, R., De Bruin, C., Appelman-Dijkstra, N. M., Winter, E. M., Oei, L., Medina-Gomez, Carolina
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.10.2021
• Subjects: Age Factors; Bone Density; Child; Epidemiology; Fractures, Bone - genetics; Genetic Loci; Genetic Predisposition to Disease; Genetics (D Karasik and C Ackert-Bicknell; Genetics (D Karasik and C Ackert-Bicknell, Section Editors); Genome-Wide Association Study; Humans; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; Multifactorial Inheritance; Orthopedics; Osteoporosis - genetics; Phenotype; Section Editors; Topical Collection on Genetics; Paediatric; Osteoporosis; Genetics; Genome-wide association studies; Children; Fracture risk
• ISSN: 1544-1873; 1544-2241; 1544-2241
• DOI: 10.1007/s11914-021-00680-0

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.