Cao Ziqin, Li Yajia, Wu Jianhuang
Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha, Hunan 410008, China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha, Hunan 410008, China.
Postgrad Med J. 2025 Jan 23;101(1192):147-155. doi: 10.1093/postmj/qgae115.
Several studies demonstrated potential associations between the telomere length (TL) in leukocytes and psoriasis or psoriatic arthritis (PsA). This study aimed to investigate whether there was the causal genetic relationship between TL and psoriatic diseases bidirectionally.
Two-sample univariable MR (UVMR) analysis was applied to explore the bidirectional causal association of TL with overall psoriasis, psoriasis vulgaris (PV) and PsA. Multivariable MR (MVMR) and the mediation effects analysis were applied to test whether the bidirectional associations between TLs and psoriasis were mediated by body mass index (BMI), alcohol, and smoking status.
According to the UVMR results, a negative causal impact of TL on the risk of overall psoriasis was found (OR = 0.775; 95% CI: 0.646-0.931; P = 6.36 × 10-3), and a similar trend was observed in the reversed direction for psoriasis-TL (IVW-β = -0.0097; 95% CI: -0.0170 to -0.0024; P = 9.12 × 10-3). There were also negative genetic associations between TL and PV bidirectionally. The independent association of genetically predicted TL and overall psoriasis persisted in the MVMR results controlled for BMI, smoking, and alcohol consumption (ORMVMR = 0.736; 95% CI: 0.597 to 0.907; P = 0.004). An independent significant association of genetic predisposition to PsA with TL was also found (βMVMR = 0.006; 95% CI: 0.001 to 0.012; P = 0.033). The mediation analysis showed that BMI partially mediated the reverse association between PSO and TL.
This MR study revealed an association between genetic indicators of shortened TL and risk of overall psoriasis and PV, and genetic predisposition to PsA was associated with longer TL. Key message What is already known on this topic? Telomere length (TL) is acknowledged to reflect an individual's biological age but is also associated with dysregulated immune function and immunosenescence. The impact of aging on psoriasis is controversial. Existing evidence suggests that aging may influence pathological changes and clinical course but whether aging is an independent risk factor remains unclear. What this study adds? The current study found an association between genetic indicators of shortened TL and the risk of overall psoriasis and psoriasis vulgaris (PV). There was a bidirectional link between genetically indicated overall psoriasis and shortened TL. A possible positive genetic association between PsA and TL was also found. How this study might affect research, practice, or policy? Our study may provide evidence for TL as new diagnostic and therapeutic strategies in clinical practices for psoriasis. Greater efforts to psoriasis management may substantially reduce the aging attributable to TL shortening. Future large-scale GWAS and experimental studies are warranted to examine the mechanistic basis for links between TL and psoriasis to improve understanding and illuminate possible therapeutic targets for psoriatic disease.
多项研究表明白细胞端粒长度（TL）与银屑病或银屑病关节炎（PsA）之间存在潜在关联。本研究旨在双向探究TL与银屑病性疾病之间是否存在因果遗传关系。
采用两样本单变量孟德尔随机化（UVMR）分析来探究TL与全身性银屑病、寻常型银屑病（PV）和PsA之间的双向因果关联。应用多变量孟德尔随机化（MVMR）和中介效应分析来检验TL与银屑病之间的双向关联是否由体重指数（BMI）、饮酒和吸烟状况介导。
根据UVMR结果，发现TL对全身性银屑病风险有负向因果影响（OR = 0.775；95%CI：0.646 - 0.931；P = 6.36×10⁻³），并且在银屑病 - TL的反向分析中观察到类似趋势（IVW - β = -0.0097；95%CI：-0.0170至 -0.0024；P = 9.12×10⁻³）。TL与PV之间也存在双向负向遗传关联。在控制了BMI、吸烟和饮酒量的MVMR结果中，遗传预测的TL与全身性银屑病的独立关联仍然存在（ORMVMR = 0.736；95%CI：0.597至0.907；P = 0.004）。还发现PsA的遗传易感性与TL存在独立的显著关联（βMVMR = 0.006；95%CI：0.001至0.012；P = 0.033）。中介分析表明BMI部分介导了银屑病（PSO）与TL之间的反向关联。
这项孟德尔随机化研究揭示了TL缩短的遗传指标与全身性银屑病和PV风险之间的关联，并且PsA的遗传易感性与较长的TL相关。关键信息 关于该主题已知的内容有哪些？端粒长度（TL）被认为可反映个体的生物学年龄，但也与免疫功能失调和免疫衰老有关。衰老对银屑病的影响存在争议。现有证据表明衰老可能影响病理变化和临床病程，但衰老是否为独立危险因素仍不清楚。本研究增加了什么内容？当前研究发现TL缩短的遗传指标与全身性银屑病和寻常型银屑病（PV）风险之间存在关联。遗传指示的全身性银屑病与TL缩短之间存在双向联系。还发现PsA与TL之间可能存在正向遗传关联。本研究可能如何影响研究、实践或政策？我们的研究可能为将TL作为银屑病临床实践中的新诊断和治疗策略提供证据。加大对银屑病管理的力度可能会大幅减少因TL缩短导致的衰老。未来有必要进行大规模全基因组关联研究（GWAS）和实验研究，以探究TL与银屑病之间联系的机制基础，从而增进理解并阐明银屑病性疾病可能的治疗靶点。
