Genetic Insights into Therapeutic Targets for Intervertebral Disc Degeneration: A Mendelian Randomization Study
نویسندگان
1 School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
2 School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
3 School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
4 Hunan key laboratory of the research and development of novel pharmaceutical preparations, School of Pharmaceutical Science, Changsha Medical University, Changsha, China
5 Hunan key laboratory of the research and development of novel pharmaceutical preparations, School of Pharmaceutical Science, Changsha Medical University, Changsha, China
6 The Hunan Provincial Key Laboratory of the TCM Agricultural Biogenomics, Changsha Medical University, Changsha, China
7 School of Medicine, Hunan Normal University School of Medicine, Changsha, China
8 School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
9 School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
10 School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
doi
10.22034/ircmj.2025.513069.2001چکیده
Background and Objectives: Intervertebral Disc Degeneration (IVDD) poses a severe threat to physical and mental health by causing intense pain, neurological damage, and a significant decline in quality of life. There is no radical treatment for disease progression, so our goal was to identify effective drug targets to address the progression of disc degeneration. Methods: In the discovery cohort, Mendelian randomization (MR) analysis was employed to identify therapeutic targets associated with IVDD. Summary statistics IVDD were obtained from two datasets: the UK Biobank and the FinnGen study. Cis-expression quantitative trait loci (cis-eQTL) data were obtained from the eQTLGen consortium and utilized as genetic instruments. Colocalization analyses were conducted to assess the likelihood that single nucleotide polymorphisms (SNPs) share common causal genetic variation with both eQTLs and IVDD. Results: MR analysis identified 28 drug targets with a causal relationship to IVDD. However, after MR analysis in the replication cohort, only six drug targets retained this causal relationship. Finally, colocalization analysis identified AKR1C2 (ORukb: 0.92; 95% CIukb: 0.89-0.95) as a potential drug target. Conclusion: Drug-target MR studies offer a promising new direction for IVDD treatment. These studies not only deepen our understanding of the pathological mechanism of IVDD, but also provide reliable targets and theoretical basis for the development of new drugs for the treatment of IVDD.
