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Genetic Association of Circulating Adipokines with Risk of Idiopathic Pulmonary Fibrosis: A Two-Sample Mendelian Randomization Study

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Abstract

Purpose

The causal relationships between circulating adipokines and idiopathic pulmonary fibrosis (IPF) are yet to be established. We performed a two-sample Mendelian randomization (MR) study to investigate the causal roles of adipokines on IPF risk.

Methods

We analyzed the summary data from genome-wide association studies (GWAS), including adiponectin, leptin, resistin and monocyte chemoattractant protein-1 (MCP-1) and IPF. The inverse-variance weighted (IVW) method was considered as the major method and the MR-Egger, weighted median, simple mode and weighted mode were utilized as complementary methods. We also performed the sensitivity analyses, including heterogeneity test, horizontal pleiotropy test and leave-one-out analysis.

Results

The selected number of single nucleotide polymorphisms (SNPs) was 13 for adiponectin, 6 for leptin,12 for resistin, and 6 for MCP-1, respectively. The results showed a causal effect of the circulating adiponectin levels on the risk of IPF (OR 0.645, 95% CI 0.457–0.911, P = 0.013). However, we did not observe significant associations of genetic changes in serum leptin (OR 1.018, 95% CI 0.442–2.346, P = 0.967), resistin (OR 1.002, 95% CI 0.712–1.408, P = 0.993), and MCP-1 (OR 1.358, 95% CI 0.891–2.068, P = 0.155) with risk of developing IPF. There was no evidence of heterogeneity or horizontal pleiotropy. The sensitivity analyses confirmed that our results were stable and reliable.

Conclusions

The increase in serum adiponectin was associated causally with a decreased risk of developing IPF. There is no evidence to support a causal association between leptin, resistin or MCP-1 with risk of IPF. Further studies are needed to confirm our findings.

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Data Availability

Publicly available datasets were analyzed in this study. All GWAS data used in this study are available in the IEU open GWAS project (https://gwas.mrcieu.ac.uk/). All data generated or analyzed during this study are included in this published article.

Abbreviations

IPF:

Idiopathic pulmonary fibrosis

MR:

Mendelian randomization

GWAS:

Genome-wide association studies

MCP-1:

Monocyte chemoattractant protein-1

IVW:

Inverse-variance weighted

MR-PRESSO:

MR pleiotropy residual sum and outlier

SNP:

Single nucleotide polymorphism

OR:

Odds ratio

95%CI:

95% Confidence interval

EMT:

Epithelial-mesenchymal transition

BMI:

Body mass index

IV:

Instrumental variable

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Acknowledgements

The authors thank all investigators and participants from the open GWAS summary datasets. Special thanks to the IEU open GWAS project developed by the MRC Integrative Epidemiology Unit (IEU) at the University of Bristol. Thank them for extracting relevant GWAS summary-level data from published articles, UK Biobank, and FinnGen biobank.

Funding

This work was supported by the Science and Technology Department of Sichuan Province (2023NSFSC1459, 2022NSFSC1313), the West China Hospital of Sichuan University Postdoctoral Science Foundation (2023HXBH043).

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Author notes

  1. Dong Huang and Linjing Gong have contributed equally to this work.

Authors and Affiliations

  1. Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, Sichuan, China

    Dong Huang, Linjing Gong & Zongan Liang

  2. Institute of Clinical Pathology, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, Sichuan, China

    Dong Huang, Linjing Gong, Zhenru Wu & Yujun Shi

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Contributions

DH and LG gave the study concept and design; all authors acquired, analyzed, and interpreted the data, and critically revised the manuscript for important intellectual content; DH drafted the manuscript; DH carried out the statistical analysis; YS and ZL supervised the study; All authors read and approved the final manuscript.

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Correspondence to Yujun Shi or Zongan Liang.

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The present study relied only on publicly available de-identified summary statistics from relevant published GWASs. The ethical approval and informed consent were obtained in all original studies. Additional ethical approval was not required for our study.

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Huang, D., Gong, L., Wu, Z. et al. Genetic Association of Circulating Adipokines with Risk of Idiopathic Pulmonary Fibrosis: A Two-Sample Mendelian Randomization Study. Lung 201, 355–362 (2023). https://doi.org/10.1007/s00408-023-00640-8

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