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Genetic Mediators of Celiac Disease and Premature Ovarian Failure: Hypothyroidism and Systemic Lupus Erythematosus

  • 0Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Journal of Reproductive Immunology +

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January 28, 2025

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January 28, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Celiac disease (CD) is linked to a 16% increased risk of premature ovarian failure (POF). Hypothyroidism and systemic lupus erythematosus (SLE) partially mediate this causal relationship, impacting women's reproductive health.

Area Of Science

  • Reproductive Endocrinology
  • Autoimmune Diseases
  • Gastroenterology

Background

  • Observational studies suggest a potential link between celiac disease (CD) and premature ovarian failure (POF).
  • The causal relationship and potential mediating factors, such as hypothyroidism and systemic lupus erythematosus (SLE), require clarification.

Purpose Of The Study

  • To investigate the causal relationship between celiac disease (CD) and premature ovarian failure (POF) using a Mendelian randomization approach.
  • To determine if hypothyroidism and SLE act as mediating factors in the association between CD and POF.

Main Methods

  • A 2-sample Mendelian randomization (2SMR) study was conducted using genome-wide association study (GWAS) summary data from the IEU OpenGWAS and FinnGen R12 databases.
  • Inverse-variance weighted (IVW) method was the primary analysis, with heterogeneity assessed using Cochran's Q.
  • Two-step MR was employed to evaluate the mediating roles of hypothyroidism and SLE, utilizing GWAS data from IEU OpenGWAS.

Main Results

  • Genetically predicted celiac disease (CD) was associated with a 16% increased risk of premature ovarian failure (POF) (OR: 1.16, 95% CI: 1.06-1.26, p = 0.001).
  • Hypothyroidism mediated 13.46% (p = 0.038) and SLE mediated 26.36% (p = 0.025) of the association between CD and POF.

Conclusions

  • Celiac disease (CD) causally increases the risk of premature ovarian failure (POF) by 16%.
  • Hypothyroidism and SLE partially mediate the causal link between CD and POF, highlighting their role in this relationship.

Keywords:

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