Assessment of bidirectional relationships between circulating cytokines and periodontitis: Insights from a mendelian randomization analysis

Shi-Jia Huang; Rong Li; Shuo Xu; Yuan Liu; Sheng-Hui Li; Sheng-Zhong Duan

doi:10.3389/fgene.2023.1124638

Assessment of bidirectional relationships between circulating cytokines and periodontitis: Insights from a mendelian randomization analysis

Front Genet. 2023 Jan 30:14:1124638. doi: 10.3389/fgene.2023.1124638. eCollection 2023.

Authors

Shi-Jia Huang^{1

2}, Rong Li³, Shuo Xu^{1

2}, Yuan Liu^{1

2}, Sheng-Hui Li³, Sheng-Zhong Duan^{1

2}

Affiliations

¹ Laboratory of Oral Microbiota and Systemic Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Shanghai Key Laboratory of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai, China.
³ MOE-Shanghai Key Laboratory of Children's Environmental Health, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

Background: The purpose of this Mendelian randomization (MR) study was to assess the causal relationship between circulating cytokines and periodontitis. Materials and methods: Based on the aggregated statistics of the largest publicly available genome-wide association study (GWAS), we applied a bidirectional two-sample MR. MR analyses were conducted using Inverse variance weighted (IVW), Robust Adjusted Profile Score (RAPS), Maximum likelihood (ML), Weighted median and MR-Egger, and results obtained from IVW served as the primary outcome. Cochran Q test was used to test the heterogeneity. MR-Egger intercept test and MR polymorphism residual and outlier test (MR-PRESSO) were used for polymorphism analysis. Leave-one-out sensitivity and funnel plots were used for sensitivity analysis. Results: The IVW method indicated that interleukin 9 (IL9) had a positive causal relationship with periodontitis [odds ratio (OR) = 1.199, 95% confidence interval (CI) = 1.049-1.372, p = 0.008], and interleukin 17 (IL17) had a negative causal relationship with periodontitis (OR = 0.847, 95% CI = 0.735-0.976, p = 0.022). In bidirectional MR, periodontitis was not causally related to any of the cytokines in our study. Conclusion: Our findings provided evidence in support of potential causal associations between circulating IL9/IL17 and periodontitis.

Keywords: IL17; IL9; cytokines; mendelian randomization; periodontitis.

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (81991503, 81991500, 81921002), the Innovative Research Team of High-Level Local Universities in Shanghai (SHSMU-ZDCX20212,500), and Clinical Research Plan of SHDC (SHDC2020CR5015).