Leukocyte telomere length and amyotrophic lateral sclerosis: a Mendelian randomization study

Orphanet Journal of Rare Diseases

Tao Huang¹  Yajun Wang²  Kailin Xia²  Linjing Zhang²  Gan Zhang²  Dongsheng Fan³ 

[1] Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China;Key Laboratory of Molecular Cardiovascular Sciences (Peking University), Ministry of Education, Beijing, China;Department of Neurology, Peking University Third Hospital, Beijing, China;Beijing Municipal Key Laboratory of Biomarker and Translational Research in Neurodegenerative Diseases, Beijing, China;Department of Neurology, Peking University Third Hospital, Beijing, China;Beijing Municipal Key Laboratory of Biomarker and Translational Research in Neurodegenerative Diseases, Beijing, China;Key Laboratory for Neuroscience, National Health Commission/Ministry of Education, Peking University, Beijing, China;

关键词: Amyotrophic lateral sclerosis;    Leukocyte telomere length;    Mendelian randomization;    Risk factors;   

DOI  :  10.1186/s13023-021-02135-2

来源: Springer

【 摘 要 】

BackgroundObservational 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.ResultsWe 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.ConclusionsOur 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.

【 授权许可】

CC BY