The Polygenic and Monogenic Basis of Paediatric Fractures.

IF 4.2 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Current Osteoporosis Reports Pub Date : 2021-10-01 Epub Date: 2021-05-04 DOI:10.1007/s11914-021-00680-0

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

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引用次数: 2

Abstract

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. 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.

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儿童骨折的多基因和单基因基础。

综述目的：骨折在儿科实践中经常发生。尽管儿童复发性骨折通常表现为单基因综合征，但儿童骨折风险可能是由影响骨密度获取的个体遗传背景决定的，因此也可能是由成人骨骼脆性决定的。在这里，我们从单基因和复杂性状遗传学的角度来研究儿科骨折。最近的发现：对儿童进行的大规模全基因组研究已经确定了约44个与骨折或骨骼特征相关的基因座，而以儿科骨折为特征的约35种单基因疾病已经被描述。基因变异可通过影响较大的单基因风险变异和影响较小的多基因风险变异导致儿童骨折。研究影响峰值骨量的遗传因素可能有助于识别早发性骨质疏松症风险较高的个体，并发现可作为骨修复药物治疗的药物靶点，以预防甚至逆转晚年的骨质流失。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current Osteoporosis Reports Medicine-Endocrinology, Diabetes and Metabolism

CiteScore

8.80

自引率

2.30%

发文量

期刊介绍： This journal intends to provide clear, insightful, balanced contributions by international experts that review the most important, recently published clinical findings related to the diagnosis, treatment, management, and prevention of osteoporosis. We accomplish this aim by appointing international authorities to serve as Section Editors in key subject areas, such as current and future therapeutics, epidemiology and pathophysiology, and evaluation and management. Section Editors, in turn, select topics for which leading experts contribute comprehensive review articles that emphasize new developments and recently published papers of major importance, highlighted by annotated reference lists. An international Editorial Board reviews the annual table of contents, suggests articles of special interest to their country/region, and ensures that topics are current and include emerging research. Commentaries from well-known figures in the field are also provided.