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May 17, 2026Medicine0 citationsOpen Access

Bidirectional Mendelian randomization study reveals no causal association between polycystic ovary syndrome and IgA nephropathy

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XWX J WangRZRui ZhangWCWeiyi Chai

Key Points

  • This study aims to explore the causal relationship between polycystic ovary syndrome (PCOS) and IgA nephropathy (IgAN) using Mendelian randomization methods.
  • Conducted bidirectional Mendelian randomization analysis using SNPs from two GWAS datasets for PCOS and IgAN.
  • Utilized inverse-variance weighted method and other sensitivity analyses.
  • Examined a total of 1424 PCOS cases versus 392,423 controls, and 15,587 IgAN cases versus 462,197 healthy controls.
  • No significant association found between PCOS and IgAN using FinnGen database SNPs (OR = 1.4405, 95% CI: 0.9907–2.0939, P = 0.05581).
  • PCOS summary statistics also showed no significant association with IgAN (OR = 1.1187, 95% CI: 0.5448–2.2972, P = 0.75988).
  • Reverse Mendelian randomization analysis indicated that IgAN does not increase the risk of PCOS (OR = 1.0473, 95% CI: 0.9871–1.1112, P = 0.1253).

Abstract

The incidence of IgA nephropathy (IgAN) is increasing, and some observational studies reported the potential correlation of polycystic ovary syndrome (PCOS) with the risk of IgAN. We performed a bidirectional Mendelian randomization analysis to determine the causal relationship between PCOS and IgAN. Single nucleotide polymorphisms (SNPs) associated with PCOS were acquired from 2 genome-wide association studies (GWAS) (FinngenR9 dataset: 1424 PCOS cases, 392, 423 controls; PCOS summary statistics dataset: 10, 074 PCOS cases, 103, 164 controls). The outcome was defined as IgAN, based on the ebi-a-GCST90018866 dataset (15, 587 IgAN cases and 462, 197 healthy controls). Inverse-variance weighted (IVW), sensitivity, and reverse Mendelian randomization analyses were conducted to determine causal relationships between PCOS and IgAN. The FinnGen database identified 3 qualified SNPs, and showed no significant association between PCOS and IgAN, as revealed by the IVW method odds ratio (OR) = 1. 4405, 95% confidence interval (CI): 0. 9907–2. 0939, P =. 05581. The PCOS summary statistics dataset identified 8 qualified SNPs, and the results showed no significant association between PCOS and IgAN, as revealed by the IVW method (OR = 1. 1187, 95% CI: 0. 5448–2. 2972, P =. 75988). Evidence from the reverse Mendelian randomization indicated that IgAN did not increase the risk of PCOS in the FinnGen database (IVW: OR = 1. 0473, 95% CI: 0. 9871–1. 1112, P =. 1253) and PCOS summary statistics (IVW: OR = 1. 021, 95% CI: 0. 9861–1. 0572, P =. 24157). Bidirectional Mendelian randomization analysis did not provide evidence supporting a causal relationship between PCOS and IgAN. However, the limited number of instrumental SNPs may constrain the statistical power to detect modest effects, and further studies are needed to explore this association.

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Cite This Study

Wang et al. (2026) studied this question.

synapsesocial.com/papers/6a095bba7880e6d24efe1a74https://doi.org/10.1097/md.0000000000048704
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