Association Between Systemic Lupus Erythematosus and Primary Hypothyroidism: Evidence from Complementary Genetic...

Area of Science:

• Genetics
• Immunology
• Endocrinology

Background:

• Systemic lupus erythematosus (SLE) and hypothyroidism frequently co-occur, but their causal link is debated.
• Observational studies suggest an association, necessitating further investigation into causality.

Purpose of the Study:

• To investigate the potential bidirectional causal relationship between SLE and primary hypothyroidism using genetic methods.
• To explore the shared genetic architecture underlying these two conditions.

Main Methods:

• Employed complementary genetic approaches: genetic correlation, Mendelian randomization (MR), and colocalization analysis.
• Utilized large-scale genome-wide association study summary statistics.
• Validated findings using independent datasets and diverse MR methodologies.

Main Results:

• Significant genetic correlation (0.2488, P = 6.00 × 10-4) indicated shared genetic structure between SLE and primary hypothyroidism.
• MR analysis revealed a bidirectional causal relationship: SLE influences hypothyroidism (OR 1.037) and hypothyroidism influences SLE (OR 1.359).
• Colocalization analysis confirmed shared causal variants, and validation analyses supported the bidirectional causality and shared loci.

Conclusions:

• Established a bidirectional causal relationship between SLE and primary hypothyroidism.
• Genetic evidence supports a shared underlying genetic basis for both conditions.