Hum Immunol. 2026 May 16;87(7):111761. doi: 10.1016/j.humimm.2026.111761. Online ahead of print.
ABSTRACT
BACKGROUND: Type 2 inflammatory diseases (T2IDs) often coexist, but their shared genetic basis remains unclear. This study explores common genetic basis between asthma and other T2IDs and identifies pleiotropic loci and mechanisms.
METHODS: Using genome-wide association study (GWAS) summary statistics, we assessed genetic correlation between asthma and four T2IDs (allergic conjunctivitis [AC], allergic rhinitis [AR], pollen allergy [PA], atopic dermatitis [AD]) via cross-trait pleiotropy analysis, followed by functional, tissue-specificity, and multi-trait colocalization analyses.
RESULTS: Significant genetic correlations were detected in all four trait pairs. Pleiotropy analysis under the composite null hypothesis (PLACO) identified 21 pleiotropic loci, with 2 colocalized (PP.H4 > 0.75). Notable pleiotropic loci were identified, such as 4q24 (MANBA, UBE2D3, and CISD2) and 19q13.2 (SNRPA, RAB4B, MIA-RAB4B, and EGLN). MAGMA revealed 49 candidate pleiotropic genes involved in synaptic structure/function and cellular organization. Tissue enrichment analysis, stratified LD score regression (S-LDSC), and summary data-based Mendelian randomization (SMR) analysis revealed that pleiotropic mechanisms play significant roles in the brain, spleen, whole blood, and EBV-transformed lymphocytes. Hyprcoloc implicated distinct lymphocyte subtypes in shared mechanisms between asthma and AD.
CONCLUSIONS: We identified shared genetic loci and gene sets between asthma and T2IDs, offering insights into genetic mechanisms and potential therapeutic targets.
PMID:42143449 | DOI:10.1016/j.humimm.2026.111761
