Genetically predicted telomere length and multiple sclerosis

Background: Previous epidemiological studies have indicated a role for telomere length in multiple sclerosis (MS) severity and phenotype. However, these studies failed to establish the causality between telomere length and MS susceptibility. Hence, we performed two-sample Mendelian randomization (MR) analysis to explore the causal relationship between telomere length and MS susceptibility. Methods: We used data of genetic variants associated with leukocyte telomere length as instrumental variables (IVs), which was identified from the largest and latest genome-wide association study (GWAS) from UK Biobank (UKB) with 472,174 participants. Summary data of MS was obtained from the International Multiple Sclerosis Genetics Consortium. We performed two-sample MR analyses using the inverse-variance weighted method as the primary approach. Other MR approaches, including the MR-Egger, the inverse variance weighted (multiplicative random effects), weighted median, simple median, weighted mode-based methods, and Causal Analysis Using Summary Effect estimates (CAUSE), were also conducted to detect the result robustness. Results: The genetic liability to longer telomere length was associated with a higher risk of MS susceptibility (odds ratio [OR] per one-SD telomere length, 1.91; 95% confidence interval [CI], 1.48-2.47; P = 8.04 x 10(-7)). The results remained consistent across multiple sensitivity analyses. Conclusions: Our study supports the causal relationship between longer telomere length and increased risk of MS susceptibility.

Automated summary

This study found a causal relationship between longer telomere length and increased risk of multiple sclerosis (MS) susceptibility through two-sample Mendelian randomization analysis.