Genetically Predicted Longer Telomere Length May Reduce Risk of Hip Osteoarthritis

Jing Yang; Huiqing Xu; Bingyue Cai; Jiahe Wei; Lingling Sun; Yasong Li; Tianle Wang; Yingjun Li

doi:10.3389/fgene.2021.718890

Genetically Predicted Longer Telomere Length May Reduce Risk of Hip Osteoarthritis

Front Genet. 2021 Oct 5:12:718890. doi: 10.3389/fgene.2021.718890. eCollection 2021.

Authors

Jing Yang¹, Huiqing Xu², Bingyue Cai², Jiahe Wei², Lingling Sun³, Yasong Li⁴, Tianle Wang⁴, Yingjun Li²

Affiliations

¹ Zhuji People's Hospital of Zhejiang Province, Zhuji Affiliated Hospital of Shaoxing University, Zhuji, China.
² School of Public Health, Hangzhou Medical College, Hangzhou, China.
³ Department of Orthopaedics, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
⁴ Department of Rheumatology and Immunology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.

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.

Keywords: hip OA; knee OA; mendelian randomization; telomere length; total OA.