Genetic analyses unravel the causal association of cytokine levels on lichen simplex chronicus risk: insights from a mendelian randomization study

Lichen simplex chronicus (LSC) presents a challenge in dermatology due to its elusive pathogenic mechanisms. While associations between circulating inflammatory cytokines and LSC were observed, the definitive causal dynamics remain to be elucidated. Our study used a two-sample Mendelian randomization (MR) approach to investigate causal relationships. We applied a suite of MR methodologies, including IVW, Weighted Median, MR-Egger, Weighted Mode, Simple Mode, MR-PRESSO, and the Steiger test, to ensure robust causal inference. Our analysis confirmed the causal impact of genetically determined cytokine levels on LSC risk, particularly MMP-10 (OR = 0.493, P = 0.004) and DNER (OR = 0.651, P = 0.043) in risk attenuation. We also found a positive causal correlation between GDNF levels (OR = 1.871, P = 0.007) and LSC prevalence. Notably, bidirectional causality was observed between DNER and LSC. Consistency across various MR analyses and sensitivity analyses confirmed the absence of horizontal pleiotropy, validating the causal estimates. This pioneering MR investigation unveils a novel genetically anchored causal relationship between the circulating levels of MMP-10, DNER, and GDNF and LSC risk. Although further validation is requisite, our findings augment the understanding of cytokine mediation in LSC and underscore prospective avenues for research.