Detecting potential causal relationship between inflammatory bowel disease and rosacea using bi-directional Mendelian randomization.

The association between rosacea and inflammatory bowel disease (IBD) has been studied in previous observational studies. It is unclear, however, whether the association is causal or not. Independent genetic variants for IBD were chosen as instruments from published Genome-wide association studies (GWAS) studies involving 38,155 cases with an IBD diagnosis and 48,485 controls in order to investigate the causal effect of IBD on rosacea. Summarized data for rosacea were gathered from various GWAS studies that included 1195 cases and 211,139 controls without rosacea. Reverse-direction Mendelian randomization (MR) analysis was done to investigate the relationship between genetically proxied rosacea and IBD. With the use of the inverse variance-weighted (IVW), MR-Egger, and weighted median approaches, a 2-sample Mendelian randomization study was carried out. Analysis of heterogeneity and sensitivity was performed to examine the pleiotropy and robustness of effect estimates. The forward-direction of the MR study was to reveal that genetic predisposition to IBD including its two main subtypes: Crohn's disease (CD) and ulcerative colitis (UC) was associated with an increased risk of rosacea. The reverse-direction MR analyses did not demonstrate that a genetic predisposition to rosacea was associated with total IBD, UC and CD. Our findings provided evidence for a causal impact of IBD, UC, and CD on rosacea, but not vice versa. The elevated incidence of rosacea in patients with IBD should be recognized by doctors to make an early diagnosis and initiate specialized therapy.

Screening for key genes associated with atopic dermatitis with DNA microarrays.

The aim of the present study was to identify key genes associated with atopic dermatitis (AD) using microarray data and bioinformatic analyses. The dataset GSE6012, downloaded from the Gene Expression Omnibus (GEO) database, contains gene expression data from 10 AD skin samples and 10 healthy skin samples. Following data preprocessing, differentially expressed genes (DEGs) were identified using the limma package of the R project. Interaction networks were constructed comprising DEGs that showed a degree of node of >3, >5 and >10, using the Osprey software. Functional enrichment and pathway enrichment analysis of the network comprising all DEGs and of the network comprising DEGs with a high degree of node, were performed with the DAVID and WebGestalt toolkits, respectively. A total of 337 DEGs were identified. The functional enrichment analysis revealed that the list of DEGs was significantly enriched for proteins related to epidermis development (P=2.95E-07), including loricrin (LOR), keratin 17 (KRT17), small proline-rich repeat proteins (SPRRs) and involucrin (IVL). The chemokine signaling pathway was the most significantly enriched pathway (P=0.0490978) in the network of all DEGs and in the network consisting of high degree­node DEGs (>10), which comprised the genes coding for chemokine receptor 7 (CCR7), chemokine ligand (CCL19), signal transducer and activator of transcription 1 (STAT1), and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1). In conclusion, the list of AD-associated proteins identified in this study, including LOR, KRT17, SPRRs, IVL, CCR7, CCL19, PIK3R1 and STAT1 may prove useful for the development of methods to treat AD. From these proteins, PIK3R1 and KRT17 are novel and promising targets for AD therapy.