GWAS of Second-Generation Antihistamine Use: Locus Specificity and Highlighted Signaling Pathways

Background Second-generation H 1 -antagonists are widely used to treat multiple allergic and non-allergic chronic conditions. Aims We aimed to identify genetic loci, locus specificity, and enriched signaling pathways associated with long-term systemic second-generation antihistamine (sgAH) use in the context of underlying diseases. Materials and Methods In FinnGen, 38,645 individuals with ≥10 sgAH purchases from Finnish pharmacies were identified, while 201,334 individuals with no such purchases served as controls. Comprehensive drug purchase records and clinical diagnoses were retrieved from national registries. Genome-wide association analysis (GWAS) of sgAH use was conducted using Regenie (17 million genotyped and imputed variants). MAGMA was employed for gene and pathway-level enrichment analysis, and phenotypic specificity of associations was evaluated using MetABF. Results In GWAS for sgAH use, we identified 67 independent loci at genome wide significance (P