Immune-mediated inflammatory diseases and leukocyte telomere length: A Mendelian randomization study

• DOI: 10.3389/fgene.2023.1129247
• Publication Date: 2023-04-17T06:00:51Z
• Authors: Meiling Liu; Ping Luo; Lihua Liu; Xianping Wei; Xue Bai; Jicui Li; Linlin Wu; Manyu Luo
• Keywords: Mendelian Randomization

Objective: To elucidate the potential causality of leukocyte telomere length (LTL) with immune-mediated inflammatory diseases (IMIDs), we conducted a Mendelian randomization (MR) study. Methods: The genetically predicted causation between LTL and IMIDs was evaluated using two-sample MR method. We analyzed 16 major IMIDs, which included systemic lupus erythematosus (SLE), bowel disease (IBD), ulcerative colitis (UC), Crohn's (CD), ankylosing spondylitis (AS), sicca syndrome (SS), rheumatoid arthritis (RA), type 1 diabetes (T1D), primary sclerosing cholangitis (PSC), idiopathic pulmonary fibrosis (IPF), atopic dermatitis (AD), sarcoidosis, hypothyroidism, hyperthyroidism, psoriasis, childhood asthma. random-effects inverse-variance weighted (IVW) method performed as main analytical approach in MR. Various sensitivity analyses, including MR-Egger, robust adjusted profile score (MR-RAPS), median, pleiotropy residual sum outlier (MR-PRESSO) methods, mode, radial plot, regression, were used to guarantee robustness results detect horizontal pleiotropy. Cochran's Q value calculated check for heterogeneity, Steiger test causal direction. Results: indicated significant inverse associations risks psoriasis (OR: 0.77, 95% CI: 0.66-0.89, p = 3.66 × 10-4), SS 0.75, 0.58-0.98, 0.03), RA 0.68-0.88, 9.85 10-5), hypothyroidism 0.84, 0.78-0.91, 7,08 10-6), hyperthyroidism 0.60, 0.44-0.83, 1.90 10-3), sarcoidosis 0.67, 0.54-0.83, 2.60 IPF 0.41, 0.29-0.58, 4.11 10-7) FinnGen observed that longer associated an increased risk AS susceptibility 1.51, 1.18-1.94, 9.66 10-4). IVW showed no relationship TL SLE 0.92, 0.62-1.38, 0.69) study; however, significantly positive correlation shown another larger GWAS 1.87, 1.37-2.54, 8.01 10-5). Conclusion: Our findings reveal abnormal has increase IMIDs. Therefore, it could be treated predictor may provide new treatment targets However, change not direct cause Further studies should aim at pathogenic mechanism or protective effects