The causal relationship between cathepsins and multiple sclerosis : a mendelian randomization study

Background Multiple sclerosis (MS) is a chronic autoimmune neurodegenerative disease. Although some evidence indicates the potential involvement of cathepsins in the MS process, the precise nature of this involvement remains uncertain. The objective of this study was to ascertain whether there is a causal relationship between cathepsins and MS. Methods This study aimed to examine the relationship between nine cathepsins and MS, incorporating heterogeneity and sensitivity analyses into the study design. The MR study was reported according to the STROBE-MR checklist. Results The MR analysis revealed a causal relationship between cathepsin H and MS (IVW: P=0.036, OR=1.095, 95% CI=1.006-1.192); and an inverse causal relationship between cathepsin E and MS (IVW: P=0.031, OR=1.043, 95% CI=1.004-1.083). Conclusion Genetically predicted risk of developing MS was associated with increased cathepsin H, whereas elevated cathepsin E was associated with developing MS, and their causal relationships were both unidirectional.