Causal associations of cytokines and growth factors with cholelithiasis: a bidirectional Mendelian randomization study

Abstract

Background: It has been reported that patients with cholelithiasis may have changes in levels of cytokines and growth factors, while their causal relationships were still unclear.

Methods: This study was a bidirectional Mendelian randomization (MR) study. Datasets of 41 circulation cytokines and growth factors and the data on cholelithiasis were obtained. Six steps of strict instrumental variable filtration were set, and inverse-variance weighted analysis, MR-Egger regression, and weighted median test were used to identify the causal relationships. Benjamini-Hochberg method was used to adjust the P-values.

Results: After adjustments of P-values, four cytokines and growth factors were still causally associated with cholelithiasis significantly: interleukin 2 receptor alpha (adjusted P: 4.59E-02), interleukin 8 (adjusted P: 1.09E-02), monocyte-specific chemokine 3 (adjusted P: 2.73E-04), and stem cell factor (adjusted P: 2.73E-04). In the reverse MR analysis, no significant causal relationship was detected after adjustment.

Conclusions: Four cytokines and growth factors, including interleukin 2 receptor alpha, interleukin 8, monocyte-specific chemokine 3, and stem cell factor, were proven to relate to cholelithiasis causally and unidirectionally.

Keywords: Mendelian randomization; cholelithiasis; cytokines; growth factors.