Shared Genetic Susceptibility Between Asthma and Immune-Mediated Inflammatory Diseases

Existing studies lack comprehensive evaluations of the genetic relationships between asthma and a broader spectrum of immune-mediated inflammatory diseases (IMIDs). This study aims to elucidate the genetic correlation and potential causal interplay between asthma and IMIDs, thereby advancing insights into their shared genetic underpinnings.

Using genome-wide association study (GWAS) data, we investigated the shared genetic relationships between asthma and IMIDs through linkage disequilibrium score regression, multitrait GWAS analysis, and genotype-tissue expression analysis.

Among 19 IMIDs, we identified significant genetic correlations between asthma and 13 IMIDs, with the strongest correlation observed with allergic rhinitis (rg = 0.665, p = 8.79 × 10^-27). Multitrait GWAS analysis and Bayesian colocalization analysis identified 15 genetic loci with pleiotropic effects, of which nine loci exhibited shared causal relationships across multiple traits, which were predominantly clustered near genes associated with immune regulation and inflammatory response. Additionally, we demonstrated tissue- and cell-type-specific enrichment of shared signals, with significant enrichment observed in the lung and spleen, as well as in B-cells.

Our findings reveal a significant genetic correlation between asthma and IMIDs. Further investigations are warranted to dissect the associations between these conditions and to elucidate the underlying mechanisms of the implicated loci.