Ankylosing spondylitis: acute/subacute vs. chronic iridocyclitis - a bidirectional two-sample Mendelian randomization study

Hui Li; Yingying Xu; Qin Guo; Tiantian Zhang; Shufen Zhou; Meimei Wu; Yuanxiong Cheng; Chengshan Guo

doi:10.3389/fimmu.2023.1295118

Ankylosing spondylitis: acute/subacute vs. chronic iridocyclitis - a bidirectional two-sample Mendelian randomization study

Front Immunol. 2024 Jan 11:14:1295118. doi: 10.3389/fimmu.2023.1295118. eCollection 2023.

Authors

Hui Li^{1

2}, Yingying Xu^{3

4}, Qin Guo², Tiantian Zhang², Shufen Zhou², Meimei Wu², Yuanxiong Cheng⁴, Chengshan Guo²

Affiliations

¹ The Third Affiliated Hospital, The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China.
² Department of Rheumatology and Immunology, The People's Hospital of Baoan Shenzhen, The Second Affiliated Hospital of Shenzhen University, Shenzhen, China.
³ Department of Intensive Care Medicine, Qingyuan People's Hospital, Qingyuan, China.
⁴ Department of Respiratory and Critical Care Medicine, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China.

Abstract

Background: Observational studies found associations between ankylosing spondylitis (AS) and iridocyclitis (IC), but the causality remained unconfirmed.

Methods: We employed two-sample Mendelian randomization (MR) to investigate the bidirectional causal relationships between AS and IC. Single-nucleotide polymorphisms (SNPs) were chosen from the FinnGen database's genome-wide association studies (GWAS) following a rigorous evaluation of the studies' quality. Sensitivity analysis was performed to assess the potential influence of pleiotropy and heterogeneity on the MR findings.

Results: Elevated genetic risk for AS showed positive causal effects on IC and its subtypes (IC, OR = 1.094, 95% CI = 1.035-1.157, P = 0.00156; Acute/Subacute IC, OR = 1.327, 95% CI = 1.266-1.392, P = 8.73×10^-32; Chronic IC, OR = 1.454, 95% CI = 1.308-1.618, P = 5.19×10^-12). Significant causal association was specifically observed between Acute/Subacute IC and AS (OR = 1.944, 95% CI = 1.316-2.873, P = 8.38×10^-4). Sensitivity analysis suggested that horizontal pleiotropy was unlikely to influence the causality, and the leave-one-out analysis confirmed that a single SNP did not drive the observed associations.

Conclusion: Our findings provide new proof of a positive causal relationship between AS and IC in the European population. Notably, it is Acute/Subacute IC, rather than IC as a whole or Chronic IC, that is associated with an elevated risk of AS. These results emphasize the significance of considering AS characteristics in the diagnosis of Acute/Subacute IC.

Keywords: Mendelian randomization; ankylosing spondylitis; causal relationship; iridocyclitis; single-nucleotide polymorphisms.

Publication types

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

MeSH terms

Genome-Wide Association Study
Humans
Iridocyclitis*
Mendelian Randomization Analysis
Spondylitis, Ankylosing* / genetics
Uveitis, Anterior*

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The study received fundings from the National Natural Science Foundation of China (No. 81270577), the Science and Technology Innovation Foundation of Shenzhen (No. JCYJ20160427191026117), the Natural Science Foundation of Guangdong Province (No. 2020A1515010458); the Construction Units of Key Specialties in Clinical Medicine of Baoan District (No. 8, 2014-2018, Health Commission of Baoan, Shenzhen City); the Youth Fund Project of Baoan People’s Hospital Group (First Hospital) (No. 2018A008, No. 2018A009), and the internal funding from Baoan People’s Hospital (2019). The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.