Allergic rhinitis (AR) is a pervasive global health issue, and currently, there is a scarcity of targeted drug therapies available. This study aims to identify potential druggable target genes for AR using Mendelian randomization (MR) analysis. MR analysis was conducted to assess the causal effect of expression quantitative trait loci (eQTL) in the blood on AR. Data on AR were collected from 2 datasets: FinnGen(R9) (11,009 cases and 359,149 controls) and UK Biobank (25,486 cases and 87,097 controls). Colocalization analysis was utilized to assess the common causal genetic variations between the identified drug target genes and AR. We also employed available genome-wide association studies (GWAS) data to gauge the impact of druggable genes on AR biomarkers and other allergic diseases. This study employs MR to analyze the relationship between 3410 druggable genes and AR. After Bonferroni correction, 10 genes were found to be significantly associated with AR risk (P < 0.05/3410). Colocalization analysis revealed a significant causal relationship between the expression variation of CFL1 and EFEMP2 genes and AR, sharing direct causal variants (colocalization probability PP.H3 + PP.H4 > 0.8), highlighting their importance as potential therapeutic targets for AR. The CFL1 gene showed a causal link with levels of thymic stromal lymphopoietin (TSLP), eosinophil count, and interleukin-13 (IL-13) (P = 0.016, 7.45E-16, 0.00091, respectively). EFEMP2 was also causally related to eosinophil count, IL-13, and interleukin-17 (IL-17) (P = 0.00012, 0.00091, 0.032, respectively). PheWAS analysis revealed significant associations of CFL1 with asthma, whereas EFEMP2 showed associations with both asthma and eczema. Protein-Protein Interaction (PPI) network analysis further unveiled the direct interactions of EFEMP2 and CFL1 with proteins related to immune regulation and inflammatory responses, with 77.64% of the network consisting of direct bindings, indicating their key roles in modulating AR-related immune and inflammatory responses. Notably, there was an 8.01% significant correlation between immune-related pathways and genes involved in inflammatory responses. These genes present notable associations with AR biomarkers and other autoimmune diseases, offering valuable targets for developing new AR therapies.

Background: Bronchopulmonary Dysplasia (BPD) is a chronic lung disease affecting preterm infants, with limited prevention and treatment options. Inhaled Nitric Oxide (iNO) is sometimes used to treat Persistent Pulmonary Hypertension of the Newborn (PPHN) and Hypoxemic Respiratory Failure (HRF), and its impact on BPD development remains debated.Objective: To assess whether iNO-related factors are potential contributors to the development of BPD Grade Ⅱ-Ⅲ in very premature infants (VPI) diagnosed with PPHN or HRF at birth using Propensity Score Matching (PSM).Methods: We conducted a retrospective cohort study of infants born at 22–32 weeks gestation with PPHN or HRF, treated with iNO for over 3 h. PSM matched groups by gestational age, birth weight, and gender, etc. Multivariate logistic regression evaluated the association between iNO treatment and BPD outcomes to identify influencing factors, while Restricted Cubic Spline (RCS) and mediation analysis examined iNO dose effects and potential mediators like mechanical ventilation time and oxygenation index (OI).Results: A higher initial iNO dose was significantly associated with a reduced risk of BPD Grade Ⅱ-Ⅲ (adjusted OR = 0.68, 95% CI: 0.52–0.89, p &lt; 0.01). Additionally, administration of iNO within the first 7 days of life was identified as an important influencing factor No significant mediation effects were observed for factors such as mechanical ventilation time and OI.Conclusion: A higher initial iNO dose within the first 7 days was associated with a reduced risk of BPD Grade Ⅱ-Ⅲ in VPI with PPHN or HRF.