Primary ovarian insufficiency consequence of autoimmune diseases: a bidirectional two-sample Mendelian randomization...

Area of Science:

• Genetics
• Immunology
• Reproductive Medicine

Background:

• Observational studies suggest a link between autoimmune disorders (AIDs) and increased primary ovarian insufficiency (POI) risk.
• The causal relationship between AIDs and POI remains unclear.
• Investigating bidirectional causality is crucial for understanding disease pathogenesis and patient management.

Purpose of the Study:

• To investigate the bidirectional causal relationship between 20 AIDs and POI.
• To utilize Mendelian randomization (MR) analysis for robust causal inference.
• To identify specific AIDs that pose a risk for developing POI.

Main Methods:

• A bidirectional two-sample MR analysis was conducted.
• Genome-wide association study (GWAS) summary-level data were used.
• Inverse variance weighted (IVW) method with sensitivity analyses (Cochran Q, MR-Egger, MR-PRESSO) was employed to ensure validity and detect pleiotropy.

Main Results:

• Systemic lupus erythematosus (SLE), coeliac disease (CeD), vitiligo, and Addison's disease (AD) showed a significant causal effect increasing POI risk.
• Selective immunoglobulin A deficiency (SIgAD) was associated with a decreased risk of POI.
• Genetically determined CeD (OR=1.124), vitiligo (OR=1.092), SLE (OR=1.122), and SIgAD (OR=0.866) demonstrated significant causal relationships with POI.

Conclusions:

• Specific AIDs, including SLE, CeD, vitiligo, and AD, causally increase POI risk.
• SIgAD is associated with a reduced risk of POI.
• Findings underscore the importance of early intervention for women with AIDs to preserve reproductive potential.