Work

A bidirectional Mendelian randomization analysis of the causal relationship between immune cells and high-grade squamous intraepithelial lesion

Year: 2025

Type: article

Abstract: High-grade squamous intraepithelial lesions (HSIL), critical precursors to cervical cancer, are associated with persistent human papillomavirus infection and immune dysregulation, yet the causal role of specific immune cell phenotypes remains unclear. To investigate bidirectional causal relationships, we performed a 2-sample Mendelian randomization (MR) analysis using European genome-wide association study data: 731 immune cell phenotypes and HSIL. Instrumental variables (P < 1 × 10⁻⁵) were selected under MR assumptions, with inverse-variance weighted as the primary method. Forward MR (immune cells to HSIL) identified 67 phenotypes nominally associated (P < .05); after FDR correction (FDR < 0.20), IgD on transitional B cells were protective, while increased CD3 on CD39+ Tregs elevated risk. Reverse MR (HSIL to immune cells) indicated HSIL causally reduces naïve CD4- CD8- T cell, HVEM on effector memory CD8+ T cells, FSC-A on lymphocyte and FSC-A on T cells (FDR < 0.20). This study provides genetic evidence for causal roles of specific immune phenotypes in HSIL pathogenesis, suggesting immunotherapeutic targets, while revealing HSIL-induced immune exhaustion patterns.

Source: Medicine

DOI: 10.1097/md.0000000000045695

Authors: Zhenyu Wang, Lu Yang, Chunxiao Li, Ping Jiang, Junjie Wang

Institutions: Peking University Third Hospital, Peking University

Language: English

Topic: Cervical Cancer and HPV Research

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,950