POS0437 GENETICALLY DETERMINED TELOMERE LENGTH AND THE RISK OF ANKYLOSING SPONDYLITIS

Abstract

BackgroundTelomeres are unique chromatin structures at the ends of eukaryotic chromosomes and play a crucial role in maintaining genomic stability. Ankylosing spondylitis(AS) is a chronic degenerative inflammatory disease that occurs primarily in the spine and sacroiliac joints. Growing evidence suggests some leukocytes in patients with AS have significantly longer telomere lengths[1]. However, whether these associations reflect a causal relationship is still being determined.ObjectivesThe aim of this study was to examine whether leukocyte telomere length is causally related to AS risk by a bidirectional Mendelian randomization (MR).MethodsTelomere length was derived from data from 472,174 participants in a genome-wide association study (GWAS); genetic associations for AS were derived from an extensive GWAS analysis that included 968 cases and 336,191 controls. SNPs were selected as instrumental variables(IVs) for significance (P < 5×10-8) and independence (r2< 0.01). In addition, body mass index (BMI), smoking, and alcohol consumption were considered to be the main confounding factors in this analysis. The causal relationship was assessed by MR analysis using the inverse variance weighting (IVW) method as the primary analysis, supplemented by the weighted median, MR-Egger[2]. The sensitivity analysis was also performed to verify the robustness of the primary results of the MR analysis. In addition, Cochran’s Q statistic was used to assess heterogeneity between SNPs in the IVW estimates.ResultsA total of 122 and 6 SNPs were selected as positive and negative IVs, respectively. Results of the IVW analysis (OR = 1.002, 95% CI: 1.000-1.003, P < 0.001) suggested a strong causality between longer telomere length and risk of AS in people of European ancestry. MR-Egger regression analysis showed that our results were not affected by multi-validity (P = 0.448). Heterogeneity analysis did not observed heterogeneity (PQ= 0.256). Further sensitivity analyses validated the robustness of the MR results. However, reverse MR analysis showed that genetically predicted AS was unrelated to telomere length(P＞0.05).ConclusionLonger telomere length is significantly associated with an increased risk of AS. Further studies are needed to elucidate the potential mechanisms underlying the role of telomeres in the development of AS.