Leukocyte telomere length and amyotrophic lateral sclerosis: a Mendelian randomization study
Abstract Background Observational studies have suggested that telomere length is associated with amyotrophic lateral sclerosis (ALS). However, whether this association is causal remains unclear. In this study, we aimed to explore the causal relationship between leukocyte telomere length (LTL) and AL...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-12-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13023-021-02135-2 |
| _version_ | 1819096143835955200 |
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| author | Kailin Xia Linjing Zhang Gan Zhang Yajun Wang Tao Huang Dongsheng Fan |
| author_facet | Kailin Xia Linjing Zhang Gan Zhang Yajun Wang Tao Huang Dongsheng Fan |
| author_sort | Kailin Xia |
| collection | DOAJ |
| description | Abstract Background Observational studies have suggested that telomere length is associated with amyotrophic lateral sclerosis (ALS). However, whether this association is causal remains unclear. In this study, we aimed to explore the causal relationship between leukocyte telomere length (LTL) and ALS by a two-sample Mendelian randomization (MR) approach. Single-nucleotide polymorphisms (SNPs) for LTL were identified through high-quality genome-wide association studies (GWASs). The ALS GWAS summary data (20,806 cases; 59,804 controls) with largest sample size to date was obtained. We adopted the inverse variance weighted (IVW) method to examine the effect of LTL on ALS and used the weighted median method, simple median method, MR Egger method and MR-PRESSO method to perform sensitivity analyses. Results We found that genetically determined increased LTL was inversely associated with the risk of ALS (odds ratio (OR) = 0.846, 95% confidence interval (CI): 0.744–0.962, P = 0.011), which was mainly driven by rs940209 in the OBFC1 gene, suggesting a potential effect of OBFC1 on ALS. The results were further confirmed by sensitivity analysis with the MR Egger method (OR = 0.647, 95% CI = 0.447–0.936, P = 0.050). Analyses by the weighted median method (OR = 0.893, P = 0.201) and simple median method (OR = 0.935, P = 0.535) also showed a similar trend. The MR Egger analysis did not suggest directional pleiotropy, with an intercept of 0.025 (P = 0.168). Neither the influence of instrumental outliers nor heterogeneity was found. Conclusions Our results suggest that genetically predicted increased LTL has a causal relationship with a lower risk of ALS. Protecting against telomere loss may be of great importance in the prevention and treatment of ALS. |
| first_indexed | 2024-12-21T23:54:31Z |
| format | Article |
| id | doaj.art-91e3668420c645199a1f030d2ea92afc |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-12-21T23:54:31Z |
| publishDate | 2021-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-91e3668420c645199a1f030d2ea92afc2022-12-21T18:45:50ZengBMCOrphanet Journal of Rare Diseases1750-11722021-12-011611810.1186/s13023-021-02135-2Leukocyte telomere length and amyotrophic lateral sclerosis: a Mendelian randomization studyKailin Xia0Linjing Zhang1Gan Zhang2Yajun Wang3Tao Huang4Dongsheng Fan5Department of Neurology, Peking University Third HospitalDepartment of Neurology, Peking University Third HospitalDepartment of Neurology, Peking University Third HospitalDepartment of Neurology, Peking University Third HospitalDepartment of Epidemiology and Biostatistics, School of Public Health, Peking UniversityDepartment of Neurology, Peking University Third HospitalAbstract Background Observational studies have suggested that telomere length is associated with amyotrophic lateral sclerosis (ALS). However, whether this association is causal remains unclear. In this study, we aimed to explore the causal relationship between leukocyte telomere length (LTL) and ALS by a two-sample Mendelian randomization (MR) approach. Single-nucleotide polymorphisms (SNPs) for LTL were identified through high-quality genome-wide association studies (GWASs). The ALS GWAS summary data (20,806 cases; 59,804 controls) with largest sample size to date was obtained. We adopted the inverse variance weighted (IVW) method to examine the effect of LTL on ALS and used the weighted median method, simple median method, MR Egger method and MR-PRESSO method to perform sensitivity analyses. Results We found that genetically determined increased LTL was inversely associated with the risk of ALS (odds ratio (OR) = 0.846, 95% confidence interval (CI): 0.744–0.962, P = 0.011), which was mainly driven by rs940209 in the OBFC1 gene, suggesting a potential effect of OBFC1 on ALS. The results were further confirmed by sensitivity analysis with the MR Egger method (OR = 0.647, 95% CI = 0.447–0.936, P = 0.050). Analyses by the weighted median method (OR = 0.893, P = 0.201) and simple median method (OR = 0.935, P = 0.535) also showed a similar trend. The MR Egger analysis did not suggest directional pleiotropy, with an intercept of 0.025 (P = 0.168). Neither the influence of instrumental outliers nor heterogeneity was found. Conclusions Our results suggest that genetically predicted increased LTL has a causal relationship with a lower risk of ALS. Protecting against telomere loss may be of great importance in the prevention and treatment of ALS.https://doi.org/10.1186/s13023-021-02135-2Amyotrophic lateral sclerosisLeukocyte telomere lengthMendelian randomizationRisk factors |
| spellingShingle | Kailin Xia Linjing Zhang Gan Zhang Yajun Wang Tao Huang Dongsheng Fan Leukocyte telomere length and amyotrophic lateral sclerosis: a Mendelian randomization study Orphanet Journal of Rare Diseases Amyotrophic lateral sclerosis Leukocyte telomere length Mendelian randomization Risk factors |
| title | Leukocyte telomere length and amyotrophic lateral sclerosis: a Mendelian randomization study |
| title_full | Leukocyte telomere length and amyotrophic lateral sclerosis: a Mendelian randomization study |
| title_fullStr | Leukocyte telomere length and amyotrophic lateral sclerosis: a Mendelian randomization study |
| title_full_unstemmed | Leukocyte telomere length and amyotrophic lateral sclerosis: a Mendelian randomization study |
| title_short | Leukocyte telomere length and amyotrophic lateral sclerosis: a Mendelian randomization study |
| title_sort | leukocyte telomere length and amyotrophic lateral sclerosis a mendelian randomization study |
| topic | Amyotrophic lateral sclerosis Leukocyte telomere length Mendelian randomization Risk factors |
| url | https://doi.org/10.1186/s13023-021-02135-2 |
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