Bidirectional Mendelian randomization analysis of causal relationships between immune cell traits and recurrent aphthous ulceration
10.12016/j.issn.2096-1456.202440381
- Author:
XIE Xuejie
1
;
XU Jun
2
;
LIU Yuan
3
;
CHEN Yue
2
;
TANG Li
2
;
GULINUER Awuti
2
Author Information
1. 1.Department of Periodontal and Mucosal, the First Affiliated Hospital of Xinjiang Medical University (the Affiliated Stomatology Hospital of Xinjiang Medical University). 2.Stomatology Disease Institute of Xinjiang Uyghur Autonomous Region
2. 1.Department of Periodontal and Mucosal, the First Affiliated Hospital of Xinjiang Medical University (the Affiliated Stomatology Hospital of Xinjiang Medical University), 2.Stomatology Disease Institute of Xinjiang Uyghur Autonomous Region
3. 1.Stomatology Disease Institute of Xinjiang Uyghur Autonomous Region 2Department of Endodontics, the First Affiliated Hospital of Xinjiang Medical University (the Affiliated Stomatology Hospital of Xinjiang Medical University).
- Publication Type:Journal Article
- Keywords:
immune phenotypes / recurrent aphthous ulcers / causal inference / Mendelian randomization / myeloid-derived suppressor cells / monocytic myeloid-derived suppressor cells / granulocytic myeloid-derived suppressor cells / single nucleotide polymorphisms / genome-wide association studies
- From:
Journal of Prevention and Treatment for Stomatological Diseases
2025;33(4):296-304
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the bidirectional causal relationship between 731 immune cell phenotypes and recurrent aphthous ulcers (RAU) using Mendelian randomization (MR).
Methods:A two-sample bidirectional MR study was conducted using publicly available genome-wide association study (GWAS) summary statistics for 731 immune cell phenotypes and the RAU GWAS summary data from the FinnGen consortium. The inverse-variance weighted (IVW) method was used as the primary analysis tool, with supplementary analyses including the weighted median (WM) method, MR-Egger regression, weighted mode, and simple mode. Sensitivity analyses were conducted using Cochran’s Q test, the mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) method for detecting pleiotropy and outliers, and leave-one-out cross-validation. Furthermore, differential analysis was performed using a clinical cohort dataset from the Gene Expression Omnibus (GEO) to further validate the MR results.
Results:In the forward MR analysis, 731 immune cell phenotypes were considered as exposures and RAU as the outcome. Among them, 52 immune cell phenotypes showed a significant causal effect on RAU (P<0.05). After false discovery rate (FDR) correction, two immune phenotypes remained significantly associated with RAU risk: with increased monocyte-derived myeloid suppressor cells (M-MDSC) (OR = 1.06; 95% CI: 1.03-1.09) and CD33 on granulocytic myeloid-derived suppressor cells (G-MDSC) (OR = 1.06; 95% CI: 1.03-1.09), the risk of RAU also increased. In reverse MR, RAU was found to have a significant causal effect on two immune cell phenotypes (P<0.05), but no significant effects were found after FDR correction. Sensitivity analysis showed no significant heterogeneity between SNPs (P>0.05). Differential analysis of the GEO dataset revealed that the characteristic genes of myeloid-derived suppressor cells (MDSC) (CTBS, IPMK, and UBA3) were significantly upregulated in RAU (P<0.05).
Conclusion:The MR results of 731 immune cell phenotypes suggest that M-MDSC and CD33 molecules on G-MDSC may be risk factors for RAU development. The clinical GEO dataset further validated that MDSC may play a role in RAU, while RAU did not show a significant causal association with the 731 immune cell phenotypes.
