Longer Telomere Length May Predict Reduced Risk for RA

Results from a meta-analysis published in Rheumatology suggest a negative causal association between telomere length (TL) and risk for rheumatoid arthritis (RA). Patients with RA were found to have significantly shorter TL compared with controls, and genetically predicted longer TL was associated with reduced risk for RA.

Investigators conducted a systematic search of PubMed, Web of Science, and the Cochrane Library from inception through April 2019 for studies related to TL and RA. Data of interest included study population, study design, sample size, assays for measuring TL length, and effect size of association between TL and RA. Study quality was assessed using the modified Newcastle-Ottawa Scale. For each study, TLs in patients with RA were normalized against TLs of controls, with standardized mean differences (SMDs) calculated for the pooled cohorts using fixed or random-effects models.

Summary statistics were extracted from prior genome-wide association studies of patients with RA. Using these statistics, investigators selected 7 TL-related single nucleotide polymorphisms (SNPs) for use as instrument variables in Mendelian randomization. The inverse-variance weighted method, the weighted-median method, and the likelihood-based method were each used to evaluate the association of genetically predicted TL with RA risk. Sensitivity analyses were performed to confirm the stability of the association between TL and RA.

A total of 11 studies were selected from meta-analysis, comprising 911 patients with RA and 2498 controls. As significant heterogeneity was observed between studies (P <.001), investigators used the random-effects model to combine effect sizes. Overall, patients with RA had significantly shorter TLs compared with controls (SMD, -0.50; 95% CI, -0.88 to -0.11; P =.012).

Among the 7 selected SNPs, 2 were nominally associated with reduced risk for RA (P =.009 and P =.006, respectively). Per the inverse-variance weighted method, having genetically predicted longer TLs was associated with a 32% reduced risk for RA (odds ratio [OR], 0.68; 95% CI, 0.54-0.86; P =.002).

The same reduced risk for RA was observed with longer TLs using the weighted-median method (OR, 0.65; 95% CI, 0.48-0.88; P =.006) and the likelihood-based method (OR, 0.68; 95% CI, 0.53-0.86; P =.002). Leave-one-out sensitivity analyses confirmed the robustness of the causal association between TL and RA.

These results suggest a causal association between longer TL and reduced risk for RA. Investigators noted that the summary-level data used for Mendelian randomization analyses were from participants of primarily European ancestry, as were the data from meta-analysis. As such, results may not be generalizable to individuals of other ethnicities. Further research is necessary to explore the mechanisms that underpin the relationship between TL and RA. 

Reference

Zeng Z, Zhang W, Qian Y, et al. Association of telomere length with risk of rheumatoid arthritis: a meta-analysis and Mendelian randomization [published online November 7, 2019]. Rheumatology (Oxford). doi: 10.1093/rheumatology/kez524