Shorter telomere length increases the risk of lymphocyte immunodeficiency: A Mendelian randomization study

Abstract

BackgroundFor a long time, the prevailing viewpoint suggests that shorter telomere contribute to chromosomal instability, which is a shared characteristic of both aging and cancer. The newest research presented that T cell immune deficiency rather than chromosome instability predisposes patients with short telomere syndromes to some cancers. However, the relationship between genetically determined telomere length (TL) and immune cells remains unclear.MethodsThe two‐sample Mendelian randomization analysis was conducted to elucidate the potential causal relationship. The genetic data of TL and immune cells were obtained from the Genome‐Wide Association Study. The inverse variance weighted (IVW) method was used to estimate the effects primarily and another four methods were as a supplement. Sensitivity analysis was used to test the results.ResultsThe IVW method showed a significant correlation between TL and the percentage of T cells in lymphocytes (odds ratio [OR]: 1.222, 95% confidence interval [CI]: 1.014–1.472, p = .035), indicating that shorter TL significantly increases the risk of low T cell percentage. Further analysis of T cell subsets indicated that shorter TL may primarily lead to a lower percentage of Natural Killer T cells (OR: 1.574, 95% CI: 1.281–1.935, p < .001). Analysis of B cell subsets revealed that shorter TL may be associated with a higher percentage of Naive‐mature B cells, and a lower percentage of Memory B cells. And the sensitivity analysis indicated the validity and robustness of our findings.ConclusionIn summary, our findings suggest that shorter TL may be associated with a decline in the percentage of T cell, as well as impediments in the differentiation of B cell, consequently leading to the onset of immunosenescence and immunodeficiency. The relevant mechanisms and potential therapeutic avenues still need further investigation.

Identification of cytokines in benign and malignant thymus tumors: based on Mendelian randomization and proteomics

“…Interrogating the causal nexus between the emergence of thymoma and discrete genetic polymorphisms unveils the underlying pathological and physiological underpinnings of thymoma, fostering enhanced comprehension of disease etiology and progression trajectories. Examination of the linkage between genetic variants and thymoma susceptibility elucidates putative targets for pharmaceutical interventions or therapeutic modalities, paving the way for customized pharmacotherapies tailored to specific genetic profiles and augmenting the efficacy of novel drug discovery endeavors (23). By using genotype as a randomization variable, MR can overcome the effects of confounding factors and reverse the causal inference of causality.…”