Causal Relationship Between Polycystic Ovary Syndrome and Autoimmune Diseases: A Two‐Sample Mendelian Randomization Study

May 19, 2025American journal of reproductive immunology (New York, N.Y. : 1989)

Possible Links Between Polycystic Ovary Syndrome and Autoimmune Diseases Using Genetic Analysis

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Abstract

IVW analysis indicated no causal relationship between PCOS and autoimmune diseases (odds ratios [OR]: 0.93-1.19, p > 0.05).

No causal inference was found for PCOS affecting autoimmune diseases (OR 0.98-1.11, p > 0.05).
Potential associations were observed between rheumatoid arthritis, Crohn's disease, and inflammatory bowel disease with PCOS (OR: 0.87-1.08, p < 0.05).
Horizontal pleiotropy was detected in the associations with rheumatoid arthritis and inflammatory bowel disease, suggesting possible bias in these results.
Findings indicate that genetically predicted PCOS is not causally linked to autoimmune diseases.

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PROBLEM: Polycystic ovary syndrome (PCOS) is known to be associated with immune response dysregulation, resembling autoimmune diseases. However, the causal relationship between PCOS and autoimmune diseases remains unclear.

METHODS: A two-sample bidirectional Mendelian randomization (MR) analysis was conducted using publicly available genome-wide association study (GWAS) data. The primary causal effects were estimated using the inverse-variance weighted (IVW) method, complemented by the weighted median, weighted mode, and MR-Egger regression approaches. Horizontal pleiotropy was assessed using MR-Egger regression and the MR pleiotropy residual sum and outlier (MR-PRESSO) method. Additionally, bidirectional MR analysis was performed to determine the directionality of causal relationships.

RESULTS: IVW analysis revealed no causal inference of PCOS on autoimmune diseases (odds ratios [OR]: 0.93-1.19, p > 0.05), and no evidence of a causal relationship was observed between autoimmune diseases and PCOS (OR 0.98-1.11, p > 0.05). These findings were further supported by the weighted median and mode methods. However, MR-Egger analysis suggested potential causal associations between rheumatoid arthritis (RA), Crohn's disease (CD), and inflammatory bowel disease (IBD) with PCOS (OR: 0.87-1.08, p < 0.05), though horizontal pleiotropy was detected for RA and IBD, indicating potential bias.

CONCLUSIONS: Genetically predicted PCOS was not causally linked to autoimmune diseases. Although potential associations between RA, CD, and IBD with PCOS were identified, these results should be interpreted cautiously due to possible pleiotropy. Future studies with larger sample sizes and advanced MR methodologies are warranted to validate these findings.

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Causal Relationship Between Polycystic Ovary Syndrome and Autoimmune Diseases: A Two‐Sample Mendelian Randomization Study

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