Genetic Factors contributing to Late Adverse Musculoskeletal Effects in Childhood Acute Lymphoblastic Leukemia Survivors (Supplemental material).

A substantial number of survivors of childhood acute lymphoblastic leukemia (ALL) suffer from treatment-related late adverse effects. While multiple studies have identified the effects of chemotherapeutics and radiation therapy on musculoskeletal outcomes, few have investigated their associations with genetic factors.<br> Here<b> </b>we analyzed musculoskeletal complications in relation to common and rare genetic variants derived through whole-exome sequencing of the PETALE cohort. Top-ranking associations were further assessed through stratified and multivariate analyses. This study identified novel genetic variants associated with long-term musculoskeletal impairments in childhood ALL survivors that might lead to personalized prophylactic or therapeutic strategies.<br>

大量儿童急性淋巴细胞白血病（acute lymphoblastic leukemia, ALL）幸存者会出现治疗相关的晚期不良反应。尽管已有多项研究阐明了化疗与放射治疗对肌肉骨骼结局的影响，但鲜有研究探讨此类影响与遗传因素之间的关联。

本研究基于PETALE队列的全外显子组测序（whole-exome sequencing）数据，分析了肌肉骨骼并发症与常见及罕见遗传变异的相关性。针对排名靠前的遗传关联，本研究进一步通过分层分析与多变量分析进行了深入评估。

本研究成功鉴定出与儿童ALL幸存者长期肌肉骨骼损伤相关的新型遗传变异，该发现可为个性化预防与治疗策略的研发提供潜在依据。