The causal relationship between 41 inflammatory cytokines and hypothyroidism: bidirectional two-sample Mendelian...

Area of Science:

• Genetics and Immunology
• Endocrinology

Background:

• Observational studies face limitations in determining causal links between inflammatory cytokines and hypothyroidism.
• Mendelian randomization (MR) offers a robust approach to investigate genetic predispositions and causal relationships.

Purpose of the Study:

• To assess the causal relationship between 41 inflammatory cytokines and hypothyroidism using a bidirectional two-sample MR analysis.
• To explore the potential role of specific cytokines in hypothyroidism pathogenesis and the impact of hypothyroidism on systemic inflammation.

Main Methods:

• Utilized a bidirectional two-sample MR analysis on data from 30,155 hypothyroidism cases and 8,293 controls of European ancestry.
• Employed inverse variance weighting (IVW), weighted median (WM), and MR-Egger methods, with sensitivity analyses including MR-PRESSO and leave-one-out tests.

Main Results:

• Identified a causal effect of Interleukin-7 (IL-7) and macrophage inflammatory protein-1β (MIP-1β) on hypothyroidism risk.
• Found evidence that hypothyroidism causally affects multiple cytokines, including IL-6, IL-7, TNF-α, and MIP-1β, indicating a systemic inflammatory response.

Conclusions:

• IL-7 and MIP-1β are implicated in hypothyroidism development, suggesting potential therapeutic targets.
• Hypothyroidism may induce a significant systemic inflammatory response, highlighting the interplay between endocrine and immune systems and potential implications for treatment.