Genetic signatures of immune cells and glucocorticoids treatment in frozen shoulder: A double-edged sword revealed by genome-wide Mendelian randomization and bulk RNA sequencing

Frozen shoulder (FS) is characterized by adhesions to the joint capsule, involving a large infiltration of immune cells. This study aimed to identify the pivotal roles of various genetic signatures of immune cells in FS for diagnosis and therapy, and to verify the consequence of widely used glucocorticoids (GCs) in FS treatment. RNA sequencing (RNA-seq) was conducted on normal and adhesive capsular tissues to identify immune cell subtypes and the expression of differential genes involved in FS. The Xcell tool was utilized to resolve the heterogeneity of the data and quantify immune cell types. Bidirectional Mendelian randomization (MR) analysis was then performed using 731 immune cell traits to determine their causal relationships with FS, with surface biomarkers verification using RNA-seq data. Additionally, the feasibility of GCs therapy for FS was assessed through causality inference using MR.