Association between type 1 diabetes mellitus and ankylosing spondylitis: a two-sample Mendelian randomization study

Ju Zhang; Jiaping Qi; Yixuan Li; Jing Wang; Huan Jiang; Qiong Sun; Qinchen Gu; Zhenhua Ying

doi:10.3389/fimmu.2023.1289104

Association between type 1 diabetes mellitus and ankylosing spondylitis: a two-sample Mendelian randomization study

Front Immunol. 2023 Dec 20:14:1289104. doi: 10.3389/fimmu.2023.1289104. eCollection 2023.

Authors

Ju Zhang^#^{1

2}, Jiaping Qi^#², Yixuan Li², Jing Wang², Huan Jiang², Qiong Sun², Qinchen Gu², Zhenhua Ying^{1

2}

Affiliations

¹ Jinzhou Medical University Graduate Training Base Zhejiang Provincial People's Hospital, Center for General Practice Medicine, Department of Rheumatology and Immunology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, China.
² Zhejiang Provincial Key Laboratory of Traditional Chinese Medicine Cultivation for Arthritis Diagnosis and Treatment, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hang zhou Medical College, Hangzhou, Zhejiang, China.

^# Contributed equally.

Abstract

Objective: The development of ankylosing spondylitis (AS) is closely related to autoimmune system dysfunction. Type 1 diabetes mellitus (T1DM) is an autoimmune disease that is a risk factor for many diseases. This study aimed to investigate the causal relationship between T1DM mellitus and AS genetically.

Methods: A genome-wide association study (GWAS) of causal relationships between exposure (T1DM) and outcome (AS) was performed using summary data from the GWAS database. We conducted a two-sample Mendelian randomization (MR) study of these two diseases. Inverse variance weighting (IVW) was used as the primary analysis method, with MR Egger, weighted median, and weighted mode used as supplementary methods. Sensitivity analyses were performed using Cochran's Q test, MR-Egger intercept, MR-Pleiotropy RESidual Sum and outlier methods, leave-one-out analysis, and funnel plots.

Results: A total of 11 single nucleotide polymorphisms (SNPs)were identified for instrumental variables(IVs) for MR analysis.IVW found that T1DM was causally associated with AS ((IVW: OR = 1.0006 (95% CI 1.0001, 1.0011), p = 0.0057; MR-Egger: OR = 1.0003 (95% CI 0.9995, 1.0012), p = 0.4147; weighted median: OR = 1.0006 (95% CI 1.0003, 1.0008), p = 0.0001; weighted mode: OR = 1.0007 (95% CI 1.0005, 1.0009), p = 0.0001). No horizontal pleiotropy was found for the MR-Egger intercept, and leave -one-out analysis found that the results remained stable after the removal of individual SNPs.

Conclusion: The results of the two-sample MR analysis supported a causal relationship between T1DM and AS risk.

Keywords: Mendelian randomization; ankylosing spondylitis; causality; risk; type 1 diabetes.

Publication types

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

MeSH terms

Autoimmune Diseases*
Diabetes Mellitus, Type 1* / genetics
Genome-Wide Association Study
Humans
Mendelian Randomization Analysis
Nonoxynol
Spondylitis, Ankylosing* / epidemiology
Spondylitis, Ankylosing* / genetics

Substances

Nonoxynol

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by grants from the Optimization of Integrated Traditional Chinese and Western Medicine Clinical Treatment Program for Rheumatoid Arthritis (RA) in Zhejiang Province(C-2020-W212).