# Identifying common genetic etiologies between iridocyclitis and related immune-mediated diseases

**Authors:** Zhao Liu, Wenqiao Zhang, Qiuyuan Wang, Xumei Du, Zhiqi Tao, Jianguo Huang, Yuqin Wang

PMC · DOI: 10.3389/fimmu.2025.1755047 · 2026-01-15

## TL;DR

This study finds genetic links between iridocyclitis and immune-mediated diseases, identifying new potential therapeutic targets.

## Contribution

The study identifies shared genetic risk loci and proteins between iridocyclitis and immune-mediated diseases using integrated GWAS analysis.

## Key findings

- Five independent iridocyclitis-related risk loci and 123 associated genes were identified.
- 14 multi-disease risk genes and 109 disease-related proteins were discovered.
- FBXL18 and IL15RA were confirmed to be responsive to inflammatory stimuli through flow cytometry.

## Abstract

Patients with iridocyclitis are at heightened risk for immune-mediated diseases. The genetic underpinnings of iridocyclitis are intricate, necessitating an integrated approach to unravel the genetic connections between iridocyclitis and these diseases.

GWAS data were integrated from three databases using METAL. Independent risk loci were analyzed through conditional and joint genome-wide multi-trait analysis, multi-marker genomic annotation, and functional mapping of significant loci. This approach combined quantitative trait loci data and various methodologies to identify genes and proteins associated with risk. Target gene verification was conducted through cell experiments and flow cytometry.

The study identified five independent iridocyclitis-related risk loci and 123 associated genes. Additionally, 14 multi-disease risk genes and 109 disease-related proteins were discovered. Flow cytometry confirms that FBXL18 and IL15RA are responsive to inflammatory stimuli and supports their role in immune-mediated pathways relevant to iridocyclitis, underscoring its potential as a therapeutic target.

This study indicates that the polygenic factors shared between iridocyclitis and immune-mediated diseases are broadly distributed across the genome. These findings affirm a genetic link between iridocyclitis and immune-mediated diseases and highlight new therapeutic targets for these conditions.

## Linked entities

- **Genes:** FBXL18 (F-box and leucine rich repeat protein 18) [NCBI Gene 80028], IL15RA (interleukin 15 receptor subunit alpha) [NCBI Gene 3601]
- **Diseases:** iridocyclitis (MONDO:0004773)

## Full-text entities

- **Genes:** IL15RA (interleukin 15 receptor subunit alpha) [NCBI Gene 3601] {aka CD215}, FBXL18 (F-box and leucine rich repeat protein 18) [NCBI Gene 80028] {aka Fbl18}
- **Diseases:** immune-mediated diseases (MESH:C567355), inflammatory (MESH:D007249), iridocyclitis (MESH:D015863)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

11 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12852376/full.md

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Source: https://tomesphere.com/paper/PMC12852376