The causal relationship between cathepsins and ankylosing spondylitis: a two-sample Mendelian randomization study

Area of Science:

• Genetics and Molecular Biology
• Immunology
• Rheumatology

Background:

• Cathepsins are key regulators in physiological processes.
• These enzymes are implicated in cancer, inflammatory, and rheumatic disorders.
• Ankylosing spondylitis (AS) is a significant inflammatory condition.

Purpose of the Study:

• To investigate the potential causal link between cathepsins and ankylosing spondylitis (AS).
• This study utilized Mendelian randomization (MR) to assess this relationship.
• Evaluating genetic associations provides insights into disease etiology.

Main Methods:

• A retrospective design was employed.
• Genetic data for cathepsins (INTERVAL study) and AS (FinnGen database) were analyzed.
• Mendelian randomization with inverse variance weighting was the primary analytical approach, with sensitivity analyses for heterogeneity and pleiotropy.

Main Results:

• Forward MR analysis indicated a potential causal association between elevated cathepsin S and increased AS risk (OR=1.08, P=0.047).
• No significant heterogeneity or pleiotropy was detected, and sensitivity analyses supported the causal inference.
• Reverse MR analysis did not reveal a significant causal effect of AS on cathepsins.

Conclusions:

• The findings suggest a possible causal role for cathepsin S in the development of ankylosing spondylitis.
• Further investigation into the mechanisms of cathepsin S in AS pathogenesis is warranted.
• This research may offer novel therapeutic targets for AS prevention and treatment.