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. 2023 Aug;201(4):355-362.
doi: 10.1007/s00408-023-00640-8. Epub 2023 Aug 2.

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

Dong Huang #  1   2 , Linjing Gong #  1   2 , Zhenru Wu  2 , Yujun Shi  3 , Zongan Liang  4
Affiliations

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

Dong Huang et al. Lung. 2023 Aug.

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.

Keywords: Adipokines; Adiponectin; Idiopathic pulmonary fibrosis; Mendelian randomization.

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