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

作者全名："Zhang, Jun"

作者地址："[Zhang, Jun] Chongqing Med Univ, Affiliated Hosp 1, Chongqing Key Lab Ophthalmol, Chongqing Eye Inst,Chongqing Branch,Natl Clin Res, Chongqing, Peoples R China"

通信作者："Zhang, J (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Chongqing Key Lab Ophthalmol, Chongqing Eye Inst,Chongqing Branch,Natl Clin Res, Chongqing, Peoples R China."

来源：JOURNAL OF INFLAMMATION RESEARCH

ESI学科分类：IMMUNOLOGY

WOS号：WOS:000755767500004

JCR分区：Q3

影响因子：4.5

年份：2022

卷号：15

期号：　

开始页：977

结束页：986

文献类型：Article

关键词：telomere length; Mendelian randomization; juvenile idiopathic arthritis; JIA-associated iridocyclitis; genetics

摘要："Background: Telomere maintenance is increasingly being considered as fundamental to the progression of immune-mediated inflammatory diseases. However, the causality underlying the purported relationship has not been fully elucidated. In the present work, we applied Mendelian randomization (MR) analysis to obtain estimates of the causal effect of telomere length (TL) on the risk of juvenile idiopathic arthritis (JIA) and JIA-associated iridocyclitis. Methods: Two-sample MR analysis was conducted using summary-level data from the largest genome-wide association studies concerning TL (78,592 individuals), JIA (6056 cases and 25,086 controls), and JIA-associated iridocyclitis (1430 cases and 9,2767 controls). All the participants were of European ancestry. The inverse variance weighted (IVW) method was applied to estimate the causal effects. Sensitivity analyses incorporating multiple complementary MR approaches were implemented to test the robustness of the association and examine potential bias from pleiotropy. Results: In our MR analysis, genetically predicted shorter TL was associated with an increased risk of JIA (IVW: odds ratio=1.68, 95% CI: 1.13-2.48, P=0.009), but not with the risk of JIA-associated iridocyclitis (IVW: odds ratio=1.75, 95% CI: 0.81-3.79, P=0.155). The other MR methods produced consistent results. Besides, a leave-one-out sensitivity analysis yielded similar findings and validated the robustness of the causal relationship. MR-Egger regression revealed no notable horizontal pleiotropy (intercept=0.046, P=0.175). Conclusion: This work provides evidence of a negative association between TL and JIA risk, but not for the association between TL and the risk of JIA-associated iridocyclitis, in a European population. Future studies with larger sample sizes are warranted to elucidate the role of TL in these diseases."

基金机构：　

基金资助正文：