A causal relationship between leukocyte telomere length and multiple sclerosis: A Mendelian randomization study

Area of Science:

• Genetics and Immunology
• Cellular Aging
• Neurodegenerative Diseases

Background:

• Multiple sclerosis (MS) is a chronic inflammatory, autoimmune, and degenerative central nervous system disorder.
• Telomeres, protective chromosomal structures, are linked to cellular aging and senescence.
• The association between leukocyte telomere length (LTL) and MS risk is not well understood.

Purpose of the Study:

• To investigate the potential causal relationship between leukocyte telomere length (LTL) and the risk of multiple sclerosis (MS).

Main Methods:

• Employed a two-sample Mendelian randomization (MR) approach.
• Utilized 12 LTL-related genetic variants as instrumental variables.
• Performed various statistical models including inverse variance weighted (IVW) and sensitivity analyses (MR-Egger, MR-PRESSO, leave-one-out).

Main Results:

• A genetically predicted shorter LTL was significantly associated with an increased risk of MS.
• The risk of MS nearly doubled with a one standard deviation decrease in genetically predicted LTL (OR = 2.00, p = 6.01e-07).
• Sensitivity analyses confirmed the robustness of the findings and indicated no significant pleiotropy.

Conclusions:

• Leukocyte telomere length (LTL) appears to have a causal effect on the risk of developing multiple sclerosis (MS).
• Shorter LTL is a potential risk factor for MS in European populations.
• LTL warrants consideration in the pathogenesis and therapeutic strategies for MS.