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Causal Association of Telomere Length and Loss of Bone: a Directional Mendelian Randomization Study of Multi-Outcomes

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机构: [1]College of Integrative Chinese and Western Medicine, Tianjin University of Traditional Chinese Medicine, No.10, Poyang Lake Road, Jinghai District, Tianjin, 301617, China. [2]Second Clinical Medical School, Guangzhou University of Traditional Chinese Medicine, No.12, Airport Road, Baiyun District, Guangzhou, 510405, Guangdong Province, China. [3]Minimally Invasive Spine Surgery, Tianjin Hospital, No.406, Jiefang South Road, Hexi District, Tianjin, 300299, China. baoshanxu99@tmu.edu.cn.
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This study employed a genome-wide association study (GWAS) to investigate the relationship between telomere length and marginal bone loss (MBL), a marker of bone health and aging. Telomere length, a biological indicator of aging, was analyzed alongside several serum markers of bone loss. Following a screen for appropriate instrumental variables, telomere length was designated as the exposure variable. We conducted the main analysis using random-effects inverse variance weighting (IVW) and supplemented it with MR Egger, weighted median, simple mode, and weighted mode analyses, employing a total of five methods. Positive outcomes underwent scrutiny through heterogeneity analysis, horizontal multiplicity analysis, and leave-one-out plot. Subsequently, the effective gene locus was chosen for a reverse MR analysis, with positive results serving as the exposure variable. We found a causal relationship between telomere length and the expression of osteocalcin (OC), matrix metalloproteinase-3 (MMP-3), and matrix metalloproteinase-12 (MMP-12), key markers of bone metabolism. Our findings suggest that telomere wear and shortening may contribute to increased activity of OC, MMP-3, and MMP-12, thus affecting bone metabolism. However, reverse Mendelian randomization analysis did not indicate a significant impact of OC, MMP-3, and MMP-12 on telomere length, implying a unidirectional relationship. Overall, this meta-analysis underscores the association between telomere length and bone loss, highlighting the importance of timing and duration of telomere wear and shortening in influencing bone metabolism.© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

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出版当年[2023]版:
大类 | 4 区 生物学
小类 | 4 区 生化与分子生物学 4 区 生物工程与应用微生物
最新[2025]版:
大类 | 3 区 生物学
小类 | 3 区 生物工程与应用微生物 4 区 生化与分子生物学
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第一作者机构: [1]College of Integrative Chinese and Western Medicine, Tianjin University of Traditional Chinese Medicine, No.10, Poyang Lake Road, Jinghai District, Tianjin, 301617, China.
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