Associations between immune cell traits and autoimmune thyroid diseases: a bidirectional two-sample mendelian...

Area of Science:

• Immunology
• Genetics
• Endocrinology

Background:

• Autoimmune thyroid diseases (AITDs), including Graves' disease (GD) and Hashimoto's thyroiditis (HT), are prevalent autoimmune disorders.
• These conditions involve aberrant immune responses directed against the thyroid gland.

Purpose of the Study:

• To investigate the causal relationship between peripheral immune cell phenotypes and the risk of AITDs using a bidirectional two-sample Mendelian randomization (MR) approach.
• To identify specific immune cell traits that may serve as potential therapeutic or diagnostic targets for AITDs.

Main Methods:

• A bidirectional two-sample MR analysis was performed using large-scale genetic datasets for immune cell phenotypes and AITDs (FinnGen, UK Biobank).
• Instrumental variables were rigorously selected and analyzed using multiple MR methods (Wald ratio, IVW, MR-Egger, weighted median).
• Sensitivity analyses (Cochrane's Q, Egger intercept, MR-PRESSO, LOO, Steiger test) were conducted to ensure result robustness and rule out reverse causation.

Main Results:

• The study identified significant associations between several immune cell phenotypes and AITD risk.
• In Graves' disease, naive CD4-CD8- (DN) T cells and terminally differentiated CD4+T cells showed significant effects.
• For Hashimoto's thyroiditis, lymphocyte count and CD45 on CD4+T cells were associated with risk. Autoimmune hypothyroidism showed associations with CD127 CD8+T cell count and terminally differentiated DN T cells.

Conclusions:

• This MR analysis provides robust genetic evidence linking specific immune cell traits to the risk of developing AITDs.
• The findings highlight potential immune cell-based biomarkers and therapeutic targets for managing AITDs.