Causal association of immune cells and polycystic ovarian syndrome: a Mendelian randomization study

Na Aru; Congyu Yang; Yuntian Chen; Jiaming Liu

doi:10.3389/fendo.2023.1326344

Causal association of immune cells and polycystic ovarian syndrome: a Mendelian randomization study

Front Endocrinol (Lausanne). 2023 Dec 22:14:1326344. doi: 10.3389/fendo.2023.1326344. eCollection 2023.

Authors

Na Aru¹, Congyu Yang¹, Yuntian Chen², Jiaming Liu³

Affiliations

¹ Department of Reproductive Endocrinology, West China Second University Hospital, Sichuan University, Chengdu, China.
² Department of Radiology, West China Hospital, Sichuan University, Chengdu, China.
³ Department of Urology, West China Hospital, Sichuan University, Chengdu, China.

Abstract

Background: Polycystic ovarian syndrome (PCOS) is a common reproductive disorder that affects a considerable number of women worldwide. It is accompanied by irregular menstruation, hyperandrogenism, metabolic abnormalities, reproductive disorders and other clinical symptoms, which seriously endangers women's physical and mental health. The etiology and pathogenesis of PCOS are not completely clear, but it is hypothesized that immune system may play a key role in it. However, previous studies investigating the connection between immune cells and PCOS have produced conflicting results.

Methods: Mendelian randomization (MR) is a powerful study design that uses genetic variants as instrumental variables to enable examination of the causal effect of an exposure on an outcome in observational data. In this study, we utilized a comprehensive two-sample MR analysis to examine the causal link between 731 immune cells and PCOS. We employed complementary MR methods, such as the inverse-variance weighted (IVW) method, and conducted sensitivity analyses to evaluate the reliability of the outcomes.

Results: Four immunophenotypes were identified to be significantly associated with PCOS risk: Memory B cell AC (IVW: OR [95%]: 1.123[1.040 to 1.213], p = 0.003), CD39+ CD4+ %CD4+ (IVW: OR [95%]: 0.869[0.784 to 0.963], p = 0.008), CD20 on CD20- CD38-(IVW: OR [95%]:1.297[1.088 to 1.546], p = 0.004), and HLA DR on CD14- CD16+ monocyte (IVW: OR [95%]:1.225[1.074 to 1.397], p = 0.003). The results of the sensitivity analyses were consistent with the main findings.

Conclusions: Our MR analysis provides strong evidence supporting a causal association between immune cells and the susceptibility of PCOS. This discovery can assist in clinical decision-making regarding disease prognosis and treatment options, and also provides a new direction for drug development.

Keywords: MR analysis; SNP; causality; immune cells; pcos.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Causality
Clinical Decision-Making
Female
Humans
Mendelian Randomization Analysis
Polycystic Ovary Syndrome* / genetics
Reproducibility of Results

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Key research and development project of Sichuan Science and Technology Department (No.2023YFS0194), National Natural Science Foundation Youth Program (No.31801066) covered the research and article publishing expenses.