The causal association between polycystic ovary syndrome and susceptibility and severity of COVID-19: a bidirectional Mendelian randomization study using genetic data

Front Endocrinol (Lausanne). 2023 Sep 8:14:1229900. doi: 10.3389/fendo.2023.1229900. eCollection 2023.

Abstract

Introduction: Observational studies have reported an association between polycystic ovary syndrome (PCOS) and COVID-19, but a definitive causal relationship has not been established. This study aimed to assess this association using two-way two-sample Mendelian randomization (MR).

Methods: A summary of PCOS characteristics was compiled using the PCOS summary statistics from the Apollo University of Cambridge Repository. COVID-19 susceptibility and severity statistics, including hospitalization and extremely severe disease, were obtained from genome-wide association studies from the COVID-19 Host Genetics Initiative. The primary analysis used the inverse variance-weighted method, supplemented by the weighted median, MR-Egger, and MR-PRESSO methods.

Results: The forward MR analysis showed no significant impact of PCOS on COVID-19 susceptibility, hospitalization, or severity (OR = 0.983, 1.011, 1.014; 95% CI = 0.958-1.008, 0.958-1.068, 0.934-1.101; and p = 0.173, 0.68, 0.733; respectively). Similarly, reverse MR analysis found no evidence supporting COVID-19 phenotypes as risk or protective factors for PCOS (OR = 1.041, 0.995, 0.944; 95% CI = 0.657-1.649, 0.85-1.164, 0.843-1.058; and p = 0.864, 0.945, 0.323; respectively). Consequently, no significant association between any COVID-19 phenotype and PCOS was established.

Conclusion: This MR study suggested that PCOS is not a causal risk factor for the susceptibility and severity of COVID-19. The associations identified in previous observational studies might be attributable to the presence of comorbidities in the patients.

Keywords: COVID-19; Mendelian randomization; SARS-CoV-2; diabetes; polycystic ovarian syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19* / complications
  • COVID-19* / epidemiology
  • COVID-19* / genetics
  • Causality
  • Female
  • Genome-Wide Association Study
  • Humans
  • Mendelian Randomization Analysis
  • Polycystic Ovary Syndrome* / epidemiology
  • Polycystic Ovary Syndrome* / genetics

Grants and funding

This study was facilitated by funding from the National Natural Science Foundation of China (General Program, 8207150903), the Chinese Clinical Medicine Innovation Center of Obstetrics, Gynecology, and Reproduction in Jiangsu Province (ZX202102), and the Postgraduate Research and Practice Innovation Program of Jiangsu Province, China (SJCX22_0770). None of these funding bodies partook in the design of the research, data collection and analysis, decision to publish, or manuscript preparation.