The First Clinical College of Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China.
Department of Orthopedic Joints, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China.
Medicine (Baltimore). 2024 Aug 16;103(33):e39324. doi: 10.1097/MD.0000000000039324.
Recent mounting evidence suggests that shortening of telomere length (TL) is associated with impaired bone health; yet, a genetic causal relationship between TL and osteonecrosis remains uncertain. This study aimed to investigate the potential causal relationship between TL and osteonecrosis using bidirectional two-sample Mendelian randomization (MR). Genome-wide association study summary statistics for TL were sourced from the IEU Open genome-wide association study project, while osteonecrosis data were obtained from the FinnGen Biobank database. A range of MR methodologies-including inverse variance weighting, MR-Egger, weighted median, simple mode, and weighted mode-were utilized for analysis, along with the MR-Egger intercept method for horizontal pleiotropy assessment, and Cochran Q and leave-one-out methods for heterogeneity testing. The forward MR analysis indicated a significant causal relationship between TL and osteonecrosis, suggesting that genetically predicted shorter TL is associated with an elevated risk of developing osteonecrosis (OR = 0.611, 95% confidence interval 0.394-0.948, P = .028). The reverse MR analysis revealed no significant influence of osteonecrosis on TL (OR = 0.999, 95% confidence interval 0.994-1.005, P = .802). Analyses for heterogeneity and horizontal pleiotropy yielded robust results. Our study demonstrates that individuals with shorter TL have an increased risk of developing osteonecrosis, whereas osteonecrosis has no effect on TL.
最近越来越多的证据表明，端粒长度（TL）缩短与骨骼健康受损有关；然而，TL 和骨坏死之间的遗传因果关系仍不确定。本研究旨在使用双向两样本 Mendelian 随机化（MR）研究 TL 和骨坏死之间的潜在因果关系。TL 的全基因组关联研究汇总统计数据来自 IEU Open 全基因组关联研究项目，而骨坏死数据来自 FinnGen 生物银行数据库。采用多种 MR 方法（包括逆方差加权、MR-Egger、加权中位数、简单模式和加权模式）进行分析，并使用 MR-Egger 截距法评估水平异质性，使用 Cochran Q 和逐个剔除方法检验异质性。正向 MR 分析表明 TL 和骨坏死之间存在显著的因果关系，表明遗传预测的较短 TL 与发生骨坏死的风险增加相关（OR=0.611，95%置信区间 0.394-0.948，P=0.028）。反向 MR 分析显示骨坏死对 TL 没有显著影响（OR=0.999，95%置信区间 0.994-1.005，P=0.802）。对异质性和水平异质性的分析得出了稳健的结果。我们的研究表明，TL 较短的个体发生骨坏死的风险增加，而骨坏死对 TL 没有影响。
