The causality between systemic inflammatory regulators and chronic respiratory diseases: A bidirectional Mendelian-randomization study

Guanyu Jiang; Weici Liu; Xiaokun Wang; Zifeng Wang; Chenghu Song; Ruo Chen; Zhao He; Huixing Li; Mingfeng Zheng; Wenjun Mao

doi:10.1016/j.cyto.2023.156470

The causality between systemic inflammatory regulators and chronic respiratory diseases: A bidirectional Mendelian-randomization study

Cytokine. 2024 Feb:174:156470. doi: 10.1016/j.cyto.2023.156470. Epub 2023 Dec 9.

Authors

Guanyu Jiang¹, Weici Liu¹, Xiaokun Wang², Zifeng Wang³, Chenghu Song¹, Ruo Chen¹, Zhao He¹, Huixing Li¹, Mingfeng Zheng⁴, Wenjun Mao⁵

Affiliations

¹ Department of Thoracic Surgery, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi 214023, Jiangsu, China.
² Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China.
³ Department of Orthopedics, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi 214023, Jiangsu, China.
⁴ Department of Thoracic Surgery, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi 214023, Jiangsu, China. Electronic address: zhengmfmedical@126.com.
⁵ Department of Thoracic Surgery, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi 214023, Jiangsu, China. Electronic address: maowenjun1@njmu.edu.cn.

PMID: 38071841
DOI: 10.1016/j.cyto.2023.156470

Abstract

Introduction: Accumulative evidence suggests the associations between systemic inflammatory regulators and chronic respiratory diseases (CRDs). However, the intrinsic causation remains implicit. Therefore, this study aimed to examine causative associations by mendelian randomization (MR) and to identify valuable active factors.

Methods: Based on data from the GWAS database, we performed MR analyses of 41 serum cytokines from 8,293 Finnish and European descent cohorts from GBMI and UKBB for five major CRDs. We mainly applied inverse variance weighted regression, supplemented by MR-Egger regression, weighted median, maximum likelihood, weighted mode, and simple mode algorithms. Moreover, sensitivity analyses were conducted using Cochrane's Q test, MR-Egger intercept, MR-PRESSO Global test and MR-Steiger filtering. Eventually, the consistency of MR results was assessed by leave-one-out.

Results: Our results suggest that 12 genetically predicted systemic inflammatory regulators probably participate in the progression of CRDs, including four risk factors (IL-1RA, IL-4, MIP-1A, PDGF-BB) and one protective factor (IL-6) in IPF, two protective factors (SCF, SDF-1A) in COPD, and two protective factors (SCF, SDF-1A) in asthma, two protective factors (GROA, IL-2RA) were also included in asthma, whereas only one factor (HGF) was protective against bronchiectasis. Additionally, two protective factors (FGF-BASIC, G-CSF) were identified in sarcoidosis. Sensitivity analyses showed no horizontal pleiotropy and significant heterogeneity. Finally, based on the findings of inverse MR analysis, no inverse causal association was uncovered, confirming the robustness of results.

Conclusion: Our study unearths potential associations between systemic inflammatory modulators and common CRDs, providing new insights for inflammation-mediated CRD prevention and therapeutic approaches.

Keywords: Chronic respiratory diseases; Cytokines; Genome-wide association study; Inflammation; Mendelian randomization.

Publication types

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

MeSH terms

Algorithms
Asthma*
Bronchiectasis*
Genome-Wide Association Study
Humans
Random Allocation
Risk Factors