Systematic Mendelian Randomization Identifies ADD1, APEH, and DLK1 as Potential Therapeutic Targets for Intervertebral Disc Degeneration

Background Intervertebral disc degeneration (IVDD) is a common chronic degenerative disease and often causes low back pain (LBP) and radiating pain in the lower extremities. Despite the variety of treatments currently available for IVDD, there is still a need to identify new therapeutic targets. Method Mendelian randomization (MR), colocalization analysis, and summary‐data‐based Mendelian randomization (SMR) were utilized to identify the potential therapeutic targets for IVDD. Cis‐expression quantitative trait loci (cis‐eQTL) data from eQTLGen Consortium, pQTL data from deCODE database, and IVDD data from FinnGen database were utilized in this study. MR was performed between druggable genes and IVDD, with colocalization analysis and SMR further confirming their relationship. Result This research identified five potential therapeutic targets for IVDD, including ADD1, APEH, CGREF1, DLK1, and NEU1. Five potential therapeutic targets were confirmed by MR, colocalization, and SMR by using the cis‐eQTL data. Five potential therapeutic targets could decrease the risk of IVDD. Moreover, there were only 3 potential therapeutic targets for IVDD after utilizing the pQTL dataset, including ADD1, APEH, and DLK1. Conclusion ADD1, APEH, and DLK1 could be the potential therapeutic targets for IVDD in the future. However, further experiments are necessary to elucidate the underlying mechanisms.