Uncovering pleiotropic loci in allergic rhinitis and leukocyte traits through multi-trait GWAS

Allergic rhinitis (AR) is a nasal inflammation triggered by the immune system's response to airborne allergens, with white blood cells playing a crucial role in the development of allergic symptoms. This study aimed to investigate the genetic correlations between AR and various blood traits in European and East Asian populations using linkage disequilibrium score regression (LDSC). By leveraging GWAS summary statistics, we identified significant genetic overlap between AR and eosinophil counts in both populations. Cross-trait analysis revealed 52 pleiotropic loci associated with AR and eosinophil counts in Europeans, while 12 novel loci were discovered in East Asians. Among these, five loci, including IL1RL1 and IL4R, were shared between Europeans and East Asians. Additionally, we identified a novel East Asian-specific locus near the CD28 gene. Differential gene expression analysis further showed that CD28 expression was significantly lower in AR patients compared to healthy controls, suggesting its potential involvement in AR pathogenesis. These findings underscore the utility of multi-trait GWAS in uncovering pleiotropic loci and provide new insights into the genetic architecture of AR, particularly emphasizing population-specific loci like CD28. This research opens avenues for understanding the genetic basis of AR and developing targeted therapies.