Exploring Causal Relationships between Leukocyte Telomere Length, Sex Hormone‐Binding Globulin Levels, and Osteoporosis Using Univariable and Multivariable Mendelian Randomization
Objective Recent evidence supports that leukocyte telomere length (LTL) may be positively associated with healthy living and inversely correlated with the risk of age‐related diseases, including osteoporosis. Furthermore, it is important to note that sex hormone‐binding globulin (SHBG) levels play a...
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| Format: | Article |
| Language: | English |
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Wiley
2024-02-01
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| Series: | Orthopaedic Surgery |
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| Online Access: | https://doi.org/10.1111/os.13947 |
| _version_ | 1797335250318131200 |
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| author | Kaibo Sun Mengying Li Yongtao Wu Yuangang Wu Yi Zeng Shengliang Zhou Linbo Peng Bin Shen |
| author_facet | Kaibo Sun Mengying Li Yongtao Wu Yuangang Wu Yi Zeng Shengliang Zhou Linbo Peng Bin Shen |
| author_sort | Kaibo Sun |
| collection | DOAJ |
| description | Objective Recent evidence supports that leukocyte telomere length (LTL) may be positively associated with healthy living and inversely correlated with the risk of age‐related diseases, including osteoporosis. Furthermore, it is important to note that sex hormone‐binding globulin (SHBG) levels play a crucial role in the regulation of osteoporosis by influencing the availability of sex hormones. Hence, this study holds significant importance as it aims to unravel the roles of LTL and SHBG levels and determine which one acts as a predominant intermediary factor in influencing osteoporosis. Using Mendelian randomization (MR), we can gain valuable insights into the intricate relationships between aging, sex hormones, and bone health. Methods Univariable and multivariable and MR analyses were employed in this study. First, we used genetic variants associated with both LTL, as determined from a study involving 472,174 European participants by Codd et al., and SHBG levels, as identified in a study conducted by Ruth et al. with 370,125 participants, as instrumental variables (IVs). Then we aimed to establish a causal relationship between LTL and SHBG levels and their potential impact on osteoporosis using univariable MR. Finally, we conducted multivariable MR to provide insights into the independent and combined effects of LTL, SHBG levels on osteoporosis risk. We used various MR methods, with the primary analysis employing the inverse‐variance weighted (IVW) model. Results Univariable MR analysis reveals a potential causal effect of longer LTL on reduced risk of osteoporosis [odds ratio (OR): 0.85; 95% confidence interval (CI): 0.73–0.99; p = 0.03]. Conversely, higher genetically determined SHBG levels affect the risk of osteoporosis positively. (OR: 1.38; 95% CI: 1.09–1.75; p < 0.01). We observed a negative causal effect for LTL on the occurrence of SHBG (OR: 0.96; 95% CI 0.94–0.98, p < 0.01). After adjustment of using multivariable MR, the causal effect of LTL on osteoporosis (OR: 0.92; 95% CI: 0.84–1.03; p = 0.14), and the effect of SHBG on osteoporosis (OR: 1.43; 95% CI: 1.16–1.75; p < 0.01) were observed. Conclusion Longer LTL may confer a protective effect against osteoporosis. Additionally, the levels of SHBG appear to play a crucial role in mediating the relationship between LTL and osteoporosis. By understanding the interplay between these factors, we can gain valuable insights into the mechanisms underlying bone health and aging and potentially identify new avenues for prevention and intervention strategies. |
| first_indexed | 2024-03-08T08:34:14Z |
| format | Article |
| id | doaj.art-5541028899474abf92e6248613a7ae99 |
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| issn | 1757-7853 1757-7861 |
| language | English |
| last_indexed | 2024-03-08T08:34:14Z |
| publishDate | 2024-02-01 |
| publisher | Wiley |
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| series | Orthopaedic Surgery |
| spelling | doaj.art-5541028899474abf92e6248613a7ae992024-02-02T01:54:27ZengWileyOrthopaedic Surgery1757-78531757-78612024-02-0116232032810.1111/os.13947Exploring Causal Relationships between Leukocyte Telomere Length, Sex Hormone‐Binding Globulin Levels, and Osteoporosis Using Univariable and Multivariable Mendelian RandomizationKaibo Sun0Mengying Li1Yongtao Wu2Yuangang Wu3Yi Zeng4Shengliang Zhou5Linbo Peng6Bin Shen7Department of Orthopedics Surgery, Orthopedic Research Institute, West China Hospital Sichuan University Chengdu ChinaCenter of Reproductive Medicine The First Affiliated Hospital of Zhengzhou University Zhengzhou ChinaWest China School of Medicine Sichuan University Chengdu ChinaDepartment of Orthopedics Surgery, Orthopedic Research Institute, West China Hospital Sichuan University Chengdu ChinaDepartment of Orthopedics Surgery, Orthopedic Research Institute, West China Hospital Sichuan University Chengdu ChinaDepartment of Orthopedics Surgery, Orthopedic Research Institute, West China Hospital Sichuan University Chengdu ChinaDepartment of Orthopedics Surgery, Orthopedic Research Institute, West China Hospital Sichuan University Chengdu ChinaDepartment of Orthopedics Surgery, Orthopedic Research Institute, West China Hospital Sichuan University Chengdu ChinaObjective Recent evidence supports that leukocyte telomere length (LTL) may be positively associated with healthy living and inversely correlated with the risk of age‐related diseases, including osteoporosis. Furthermore, it is important to note that sex hormone‐binding globulin (SHBG) levels play a crucial role in the regulation of osteoporosis by influencing the availability of sex hormones. Hence, this study holds significant importance as it aims to unravel the roles of LTL and SHBG levels and determine which one acts as a predominant intermediary factor in influencing osteoporosis. Using Mendelian randomization (MR), we can gain valuable insights into the intricate relationships between aging, sex hormones, and bone health. Methods Univariable and multivariable and MR analyses were employed in this study. First, we used genetic variants associated with both LTL, as determined from a study involving 472,174 European participants by Codd et al., and SHBG levels, as identified in a study conducted by Ruth et al. with 370,125 participants, as instrumental variables (IVs). Then we aimed to establish a causal relationship between LTL and SHBG levels and their potential impact on osteoporosis using univariable MR. Finally, we conducted multivariable MR to provide insights into the independent and combined effects of LTL, SHBG levels on osteoporosis risk. We used various MR methods, with the primary analysis employing the inverse‐variance weighted (IVW) model. Results Univariable MR analysis reveals a potential causal effect of longer LTL on reduced risk of osteoporosis [odds ratio (OR): 0.85; 95% confidence interval (CI): 0.73–0.99; p = 0.03]. Conversely, higher genetically determined SHBG levels affect the risk of osteoporosis positively. (OR: 1.38; 95% CI: 1.09–1.75; p < 0.01). We observed a negative causal effect for LTL on the occurrence of SHBG (OR: 0.96; 95% CI 0.94–0.98, p < 0.01). After adjustment of using multivariable MR, the causal effect of LTL on osteoporosis (OR: 0.92; 95% CI: 0.84–1.03; p = 0.14), and the effect of SHBG on osteoporosis (OR: 1.43; 95% CI: 1.16–1.75; p < 0.01) were observed. Conclusion Longer LTL may confer a protective effect against osteoporosis. Additionally, the levels of SHBG appear to play a crucial role in mediating the relationship between LTL and osteoporosis. By understanding the interplay between these factors, we can gain valuable insights into the mechanisms underlying bone health and aging and potentially identify new avenues for prevention and intervention strategies.https://doi.org/10.1111/os.13947Leukocyte telomere lengthMendelian randomizationOsteoporosisSex hormone‐binding globulin |
| spellingShingle | Kaibo Sun Mengying Li Yongtao Wu Yuangang Wu Yi Zeng Shengliang Zhou Linbo Peng Bin Shen Exploring Causal Relationships between Leukocyte Telomere Length, Sex Hormone‐Binding Globulin Levels, and Osteoporosis Using Univariable and Multivariable Mendelian Randomization Orthopaedic Surgery Leukocyte telomere length Mendelian randomization Osteoporosis Sex hormone‐binding globulin |
| title | Exploring Causal Relationships between Leukocyte Telomere Length, Sex Hormone‐Binding Globulin Levels, and Osteoporosis Using Univariable and Multivariable Mendelian Randomization |
| title_full | Exploring Causal Relationships between Leukocyte Telomere Length, Sex Hormone‐Binding Globulin Levels, and Osteoporosis Using Univariable and Multivariable Mendelian Randomization |
| title_fullStr | Exploring Causal Relationships between Leukocyte Telomere Length, Sex Hormone‐Binding Globulin Levels, and Osteoporosis Using Univariable and Multivariable Mendelian Randomization |
| title_full_unstemmed | Exploring Causal Relationships between Leukocyte Telomere Length, Sex Hormone‐Binding Globulin Levels, and Osteoporosis Using Univariable and Multivariable Mendelian Randomization |
| title_short | Exploring Causal Relationships between Leukocyte Telomere Length, Sex Hormone‐Binding Globulin Levels, and Osteoporosis Using Univariable and Multivariable Mendelian Randomization |
| title_sort | exploring causal relationships between leukocyte telomere length sex hormone binding globulin levels and osteoporosis using univariable and multivariable mendelian randomization |
| topic | Leukocyte telomere length Mendelian randomization Osteoporosis Sex hormone‐binding globulin |
| url | https://doi.org/10.1111/os.13947 |
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