Causal relationship between polycystic ovary syndrome and chronic kidney disease: A Mendelian randomization study

Front Endocrinol (Lausanne). 2023 Mar 15:14:1120119. doi: 10.3389/fendo.2023.1120119. eCollection 2023.

Abstract

Objective: Polycystic ovary syndrome is one of the most common endocrine disorders among women of childbearing age. The relationship between polycystic ovary syndrome and chronic kidney disease remains unclear and controversial. In this study, we investigated the causal role of polycystic ovary syndrome in the development of chronic kidney disease using the two-sample Mendelian randomization method.

Methods: Public shared summary-level data was acquired from European-ancestry genome wide association studies. We finally obtained 12 single nucleotide polymorphisms as instrumental variables, which were associated with polycystic ovary syndrome in European at genome-wide significance (P < 5 × 10-8). Inverse-variance weighted method was employed in the Mendelian randomization analysis and multiple sensitivity analyses were implemented. Outcome data were obtained from the Open GWAS database.

Results: A positive causal association was observed between polycystic ovary syndrome and chronic kidney disease (odds ratio [OR]=1.180, 95% confidence interval [CI]: 1.038-1.342; P=0.010). Further analyses clarified that causal relationship exist between polycystic ovary syndrome and some serological indicators of chronic kidney disease (fibroblast growth factor 23: OR= 1.205, 95% CI: 1.031-1.409, P=0.019; creatinine: OR= 1.012, 95% CI: 1.001-1.023, P=0.035; cystatin C: OR= 1.024, 95% CI: 1.006-1.042, P=0.009). However, there was no causal association of polycystic ovary syndrome with other factors in the data sources we employed.

Conclusions: Our results indicate an important role of polycystic ovary syndrome in the development of chronic kidney disease. This study suggests that regular follow-up of renal function in patients with polycystic ovary syndrome is necessary for the early treatment of chronic kidney disease.

Keywords: Mendelian randomization; causality; chronic kidney disease; polycystic ovary syndrome; single nucleotide polymorphisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Causality
  • Female
  • Genome-Wide Association Study
  • Humans
  • Mendelian Randomization Analysis / methods
  • Polycystic Ovary Syndrome* / complications
  • Polycystic Ovary Syndrome* / epidemiology
  • Polycystic Ovary Syndrome* / genetics
  • Renal Insufficiency, Chronic* / etiology
  • Renal Insufficiency, Chronic* / genetics

Grants and funding

This work was supported by the National Natural Science Foundation of China (81830025, 81620108004); we acknowledge the support of the National Key R&D Program of China 2019YFA0802502, and Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-030A).