Genetic correlation between chronic sinusitis and autoimmune diseases.

Objective: The association between autoimmune diseases and chronic rhinosinusitis in observational studies remains unclear. This study aimed to explore the genetic correlation between chronic rhinosinusitis and autoimmune diseases.

Methods: We employed Mendelian randomization (MR) analysis and linkage disequilibrium score regression (LDSC) to investigate causal relationships and genetic correlations between autoimmune phenotypes and chronic rhinosinusitis. Additionally, transcriptome-wide association (TWAS) analysis was conducted to identify the shared genes between the two conditions to demonstrate their relationship. The CRS GWAS (genome-wide association study) data and other autoimmune diseases were retrieved from ieuOpenGWAS (https://gwas.mrcieu.ac.uk/), the FinnGen alliance (https://r8.finngen.fi/), the UK Biobank (https://www.ukbiobank.ac.uk/), and the EBI database (https://www.ebi.ac.uk/).

Results: Utilizing a bivariate two-sample Mendelian randomization approach, our findings suggest a significant association of chronic rhinosinusitis with various autoimmune diseases, including allergic rhinitis ( = 9.55E-10, Odds Ratio [OR] = 2,711.019, 95% confidence interval [CI] = 261.83391-28,069.8), asthma ( = 1.81E-23, OR = 33.99643, 95%CI = 17.52439-65.95137), rheumatoid arthritis ( = 9.55E-10, OR = 1.115526, 95%CI = 1.0799484-1.1522758), hypothyroidism ( = 2.08828E-2, OR = 4.849254, 95%CI = 1.7154455-13.707962), and type 1 diabetes ( = 2.08828E-2, OR = 01.04849, 95%CI = 1.0162932-1.0817062). LDSC analysis revealed a genetic correlation between the positive autoimmune phenotypes mentioned above and chronic rhinosinusitis: AR (rg = 0.344724754,  = 3.94E-8), asthma (rg = 0.43703672,  = 1.86E-10), rheumatoid arthritis (rg = 0.27834931,  = 3.5376E-2), and hypothyroidism (rg = -0.213201473,  = 3.83093E-4). Utilizing the Transcriptome-Wide Association Studies (TWAS) approach, we identified several genes commonly associated with both chronic rhinosinusitis and autoimmune diseases. Genes such as TSLP/WDR36 (Chromosome 5, top SNP: rs1837253), ORMDL3 (Chromosome 13, top SNP: rs11557467), and IL1RL1/IL18R1 (Chromosome 2, top SNP: rs12905) exhibited a higher degree of consistency in their shared involvement across atopic dermatitis (AT), allergic rhinitis (AR), and chronic rhinosinusitis (CRS).

Conclusion: Current evidence suggests a genetic correlation between chronic rhinosinusitis and autoimmune diseases like allergic rhinitis, asthma, rheumatoid arthritis, hypothyroidism, and type 1 diabetes. Further research is required to elucidate the mechanisms underlying these associations.