Inflammatory proteins and hidradenitis suppurativa: Insights from genetic correlation and Mendelian randomization

Abstract

Previous research has highlighted a significant association between inflammatory proteins and the development and progression of hidradenitis suppurativa (HS). Nevertheless, the potential causative link between these factors remains to be definitively established. To investigate the genetic correlation between inflammatory proteins and HS, linkage disequilibrium score regression (LDSC) was employed. Mendelian randomization (MR) analysis, incorporating inverse variance weighted, MR-Egger, and weighted median methodologies, was utilized to evaluate the possible causal relationship between circulating inflammatory proteins (CIPs) and HS. Additionally, reverse MR analysis was carried out to explore reverse causality. The data set for 91 CIPs was derived from a genome-wide protein quantitative trait loci study, while HS-related data were acquired from the FinnGen study. Moreover, the stability of the causal relationships was assessed via sensitivity analyses, encompassing tests for pleiotropy, heterogeneity, and leave-one-out analysis. The LDSC analysis suggested the existence of genetic correlations between the levels of Fibroblast growth factor 21 (FGF-21), stem cell factor, and HS. The MR analysis identified a suggestive association of T-cell surface glycoprotein CD5 and C-X-C motif chemokine 11 with an elevated risk of HS. Conversely, C-C motif chemokine 4, Protein S100-A12, Interleukin-10 receptor subunit beta, and Programmed cell death 1 ligand 1 were associated with a diminished risk of HS. Moreover, HS was demonstrated to increase the levels of four CIPs: Interleukin-20, Leukemia inhibitory factor (LIF), LIF receptor, and Thymic stromal lymphopoietin. The findings of this investigation offer suggestive evidence for possible genetic correlations and causal links between various genetically predicted inflammatory proteins and HS. There exists a pressing requirement for additional studies to elucidate the fundamental processes driving these associations.