Genetic association between ankylosing spondylitis and major depressive disorders: Shared pathways, protein networks and the key gene

Abstract

The prevalence of ankylosing spondylitis (AS) and major depressive disorders (MDD) becomes increasingly pronounced, exerting a significant impact on the life quality of contemporary people. Although there is mounting evidence of a link between AS and major depression disorders, the specific interactions between the two have not been thoroughly investigated. To this end, this study aimed to check whether the gene expression profiles of patients with AS and major depression disorders overlapped, and whether there were any functional links between the identified genes via protein–protein interactions. Herein, the relationship between the 4 datasets (GSE73754, GSE98793, GSE25101, and GSE54564) chosen from the Gene Expression Omnibus for evaluation and validation was investigated using gene characterization and functional enrichment. Then, following Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes that explore the biological processes of common genes and demonstrate the interrelationships between common genes, hub genes were obtained using the STRING database and the application cytoHubba plugin of Cytoscape software. The correlation between the gene and 22 types of immuno-infiltrating cells was explored, and the key gene as well as the diagnostic efficiency of the key gene was obtained through verification. A total of 204 shared genes were discovered, the majority of which were functionally enriched in Ribosome, Coronavirus disease COVID19, Starch and sucrose metabolism, and Galactose metabolism. Then, efforts were made to go through STRING. Immuno-infiltration studies revealed that Neutrophils, T cells CD8, T cells CD4 naive, T cells CD4 memory resting, T cells CD4 memory activated, and T cells regulatory were associated with the pathogenesis of AS and MDD. Additionally, the receiver operating characteristic curve revealed that the key gene MRPL13 played diagnostic roles in AS and MDD after intersecting 10 hub genes with 37 differential expression genes from the 2 validation datasets. The obtained results suggest an overlapping genetic structure between AS and major depression disorders. MRPL13 may provide key insights into the relationship between AS and MDD.