The Genetic Association Identified Between Intervertebral Disc Degeneration and Associated Risk Factors Based on a Systems Biology Approach

Study design: Genetic cross-over study of intervertebral disc degeneration (IDD) and its associated risk factors.

Objective: The purpose is to identify molecular biomarkers that may be involved in the IDD process and to provide effective recommendations in combination with drug analysis via systems biology methods.

Summary of background data: The pathogenesis and genetic links of IDD are still unclear. Related research is mainly based on a single data set or gene, and the impact of related risk factors on IDD is often ignored.

Methods: Identifying disease-associated biomarkers and therapeutic targets through a systems biology approach that Integrative network-based gene and multi-omics analysis. In this study, the differential expression of genes was analyzed through NCBI datasets, followed by enrichment analysis. The central protein was identified through the establishment of protein-protein interaction (PPI) network. Key genes were screened out by VENN diagram and reasonable suggestions were put forward based on gene-chemical drug analysis.

Results: The IDD database analysis revealed 669 differentially expressed genes (DEGs) which were 22, 26, 168, 5, 38, 36, and 16 common DEGs with AG, SM, DEP, NAD, CED, OB, and HFD, respectively. GO and KEGG enrichment analysis may reveal the pathway by which these DEGs were involved. PPI network identified 10 central proteins including CCNB1, RETN, HMMR, BUB1, MPO, OIP5, HP, KIF11, BUB1B, and CDC25A. Three key genes BUB1, BUB1B, and CCNB1 were screened out and their expression might be related to the pathogenesis of IDD. According to the three chemical Dexamethasone, Nicotine, and Resvera-trol obtained from the analysis of genes-chemical drugs, reasonable treatment suggestions were put forward.

Conclusion: Genetic association between IDD and risk factors in the general population was revealed by association network. Important gene-related molecular pathways and chemical drugs closely related to IDD have been found. Further study can provide guidance for the treatment and prognosis of IDD.Level of Evidence: N/A.