Abstract
Background
Increased inflammation in the liver during ethanol exposure is a major feature of alcoholic liver disease (ALD). An important contributing component to the development of ALD is the inflammatory response brought on by immunological response, however the connection between individual circulating cytokines and ALD is still unclear. To ascertain the causation, we conducted a two-sample bidirectional Mendelian randomization research.
Methods
We extracted 41 cytokines and growth factors of 8293 Europeans and ALD cases of the same ethnicity (1416 cases and 217,376 controls) from the Genome-Wide Association Studies (GWAS) database for two-sample bidirectional MR analysis.
Results
Our analyses suggest that higher interleukin-7 (IL-7) levels are associated with an increased risk of ALD (p = 0.028, OR = 1.191,95% CI = 1.019–1.392), while tumor necrosis factor related apoptosis inducing ligand (TRAIL) is a protective factor for ALD (p = 0.032, OR = 0.863, 95% CI = 0.754–0.988) which can reduce the risk of disease occurrence. In addition, genetically predicted ALD does not affect the expression of circulating cytokines regulators.
Conclusions
Our study supports that cytokines play a pivotal role in the pathogenesis of ALD. To determine the mechanisms and pathways of action of these biomarkers, further basic research is required to ensure their clinical suitability for preventing and treating ALD.
Acknowledgments
We thank all the researchers in this MR study. The Data on ALD, and circulating cytokines were searched from GWAS data, we thank all investigators.
Authors contributions
DW, OYH and WYH contributed to conception and design of the study. DW, OYH, WYH, LKB and ZRW performed the statistical analysis. DW wrote the first draft of the manuscript. JFZ and HYW made conceptualization and guidance of the overall article. All authors contributed to manuscript revision, read, and approved the submitted version.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Data availability statement
The data presented in this study are openly available in MRC IEU Open GWAS database (https://gwas.mrcieu.ac.uk/). Data on circulating cytokines at PMID: 27989323 and ALD from FinnGen at opengwas id:finn-b-ALCOLIVER