Genetically Predicted Longer Telomere Length May Reduce Risk of Hip Osteoarthritis

Abstract

Objective: This two-sample Mendelian randomization (MR) study aimed to examine the potential causal association of telomere length (TL) with the risk of osteoarthritis (OA).Method: The summary-level data for OA was derived from the United Kingdom Biobank cohort, including 50,508 individuals of European descent. Eighteen single nucleotide polymorphisms associated with TL were identified as instrumental variables from the most up-to-date TL genome-wide association study (GWAS) involving over 78,592 individuals of European descent. Based on the GWASs data, MR was performed using established statistical analysis methods including the inverse variance weighted, weighted median, MR-Egger, and MR pleiotropy residual sum and outlier.Results: Genetically determined TL was not associated with the risk of total OA (IVW odds ratio [OR] = 1.00, 95% confidence interval [CI] = 0.83, 1.21). In subgroup analyses stratified by OA site, no evidence in favor of association between genetically determined TL and knee OA was found (IVW OR = 1.18, 95% CI = 0.89, 1.58). However, using WM method, we observed a limited protective effect of longer TL on the risk of hip OA (OR = 0.60, 95% CI = 0.36–0.99), whereas the results of the IVW (p = 0.931) and MR-PRESSO (p = 0.932) showed that TL had no effect on hip OA.Conclusions: This study does not support a causal association between TL and total OA. A potential protective association between longer TL and hip OA, though possible, remains less certain.

Mendelian Randomization Study Implies Causal Linkage Between Telomere Length and Juvenile Idiopathic Arthritis in a European Population

“…Furthermore, our results are in keeping with a causal role of shortened TL in increasing the risk of multiple immune-mediated disorders such as rheumatoid arthritis and hip osteoarthritis, as discovered in a growing number of MR studies. 6 , 41 Although the exact role of TL in JIA has not yet been clearly defined, these findings suggest that telomere attrition seems to be a common trait of these disorders. Thus, the modulation of TL, except for a better understanding of various TL analyses, may represent a potential therapeutic approach for taking control of a disease risk.…”

Potential Methods of Targeting Cellular Aging Hallmarks to Reverse Osteoarthritic Phenotype of Chondrocytes

“…Shorter telomere length was detected in chondrocytes isolated from articular cartilage of older adults as well as OA-affected cartilage, which was associated with proximity to lesions, OA severity, and senescence level [ 54 , 55 ]. In addition, shorter telomere length of chondrocytes is found to be associated with poorer physical performance in patients with knee OA [ 56 ], while longer telomere length may reduce the risk of hip OA [ 57 ]. Mechanistically, replication-dependent telomere shortening alone does not apply to cells with low to absent mitotic activity such as chondrocytes [ 50 ].…”