Causal relationship between inflammatory cytokines and autoimmune thyroid disease: a bidirectional two-sample...

Area of Science:

• Immunology
• Genetics
• Endocrinology

Background:

• Autoimmune thyroid disease (AITD) is common, with inflammatory cytokines implicated in its pathology.
• The precise causal relationship between specific inflammatory cytokines and AITD subtypes (Graves' disease and Hashimoto's thyroiditis) requires further elucidation.

Approach:

• A two-sample Mendelian randomization (MR) analysis was conducted to assess bidirectional causal relationships between AITD and 41 inflammatory cytokines.
• Genetic instrumental variables for cytokines were obtained from the FinnGen biobank, and AITD GWAS data were sourced from meta-analyses.
• Standard MR methods (inverse variance-weighted, MR-Egger, weighted median) and sensitivity analyses were employed.

Key Points:

• Seven causal associations were identified between inflammatory cytokines and AITD. Elevated tumor necrosis factor-β and reduced stem cell growth factor-β were linked to increased Graves' disease risk.
• Increased interleukin-12p70 (IL-12p70), IL-13, interferon-γ, and decreased monocyte chemotactic protein-1 (MCP-1) and TNF-α were associated with higher Hashimoto's thyroiditis risk.
• Graves' disease was associated with increased levels of several cytokines including MCP-1 and interferon γ-induced protein 10 (IP-10), while Hashimoto's thyroiditis was linked to elevated monokine induced by interferon-γ (MIG) and IL-16.

Conclusions:

• Bidirectional MR analysis confirms a causal interplay between inflammatory cytokines and autoimmune thyroid disease.
• These findings provide crucial insights into the underlying pathophysiological mechanisms of AITD, potentially informing future therapeutic strategies.