Negative causal exploration of systemic sclerosis: a Mendelian randomization analysis

Area of Science:

• Genetics
• Immunology
• Epidemiology

Background:

• Systemic sclerosis (SSc) is an autoimmune disease with unknown causes.
• Previous studies suggest potential links between SSc and thyroid disease or appendicitis.
• Investigating these associations can clarify SSc pathophysiology.

Purpose of the Study:

• To determine if appendicitis or thyroid diseases (autoimmune thyroiditis, Graves' disease, hypothyroidism) causally influence the risk of developing Systemic Sclerosis (SSc).
• To assess if SSc influences the risk of developing thyroid disease.
• To explore potential genetic associations in SSc development.

Main Methods:

• Mendelian randomization (MR) analysis was performed using two cohorts.
• Instrumental variables (IVs) based on single nucleotide polymorphisms (SNPs) were utilized.
• Multiple MR methods (MR-IVW, MR-Egger, weighted median) and sensitivity analyses were employed to ensure robust findings.

Main Results:

• No significant causal association was found between appendicitis and SSc.
• No significant causal associations were observed between autoimmune thyroiditis, Graves' disease, or hypothyroidism and SSc.
• Reverse MR analysis indicated no significant causal effect of SSc on thyroid disease.

Conclusions:

• Appendicitis and common thyroid diseases do not appear to be causal risk factors for Systemic Sclerosis.
• SSc does not appear to be a causal risk factor for thyroid disease.
• These findings help elucidate the complex etiology of SSc and its relationship with other autoimmune and inflammatory conditions.