Casual Effects of Telomere Length on Sarcoidosis: A Bidirectional Mendelian Randomisation Analysis

Abstract

Abstract Background Telomere length (TL), crucial for genomic stability, have been implicated in various inflamm-aging diseases, but their role in sarcoidosis remains unexplored. Objective This study aims to explore the casual effects between TL and sarcoidosis via a bidirectional Mendelian Randomization (MR) study. Methods We examined single nucleotide polymorphisms (SNPs) associated with TL and sarcoidosis, utilizing available open-access genome-wide association study (GWAS) databases from the UK Biobank and FinnGen. We employed five MR techniques, including Inverse Variance Weighted (IVW), MR Egger, weighted median (WM), Robust adjusted profile score (RAPS), and Maximum likelihood, to assess causal relationships and explore pleiotropy. Results Summary data extracted from GWAS datasets of TL (n = 472,174) and (n = 217,758) of European ancestry. Employing 130 SNPs with genome-wide significance as instrumental factors for TL, we detect a significant negative correlation between TL and sarcoidosis (OR: 0.682, 95% confidence interval: 0.524–0.888,p:0.0045). Similarly, utilizing 6 SNPs with genome-wide significance as instrumental factors for sarcoidosis, we fail to identify a noteworthy association between sarcoidosis and TL (OR:0.992, 95% confidence interval: 0.979–1.005, p: 0.2424). Conclusion Our results suggest that longer telomeres may reduce the risk of sarcoidosis, highlighting TL as a potential biomarker for diagnosis and long-term monitor. This study contributes to understanding the genetic interplay between TL and sarcoidosis and opens new avenues for prevention and therapeutic interventions.