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Genome-wide association studies (GWASs) have identified single nucleotide polymorphisms (SNPs) in chr11p15.5 region associated with asthma and idiopathic interstitial pneumonias (IIPs). We sought to identify functional genes for asthma by combining SNPs and mRNA expression in bronchial epithelial cells (BEC) in the Severe Asthma Research Program (SARP). Correlation analyses of mRNA expression of six candidate genes ( AP2A2 ,  MUC6 ,  MUC2 ,  MUC5AC ,  MUC5B , and  TOLLIP ) and asthma phenotypes were performed in the longitudinal cohort ( n  = 156) with RNAseq in BEC, and replicated in the cross-sectional cohort ( n  = 155). eQTL ( n  = 114) and genetic association analysis of asthma severity (426 severe vs. 531 non-severe asthma) were performed, and compared with previously published GWASs of IIPs and asthma. Higher expression of  AP2A2  and  MUC5AC  and lower expression of  MUC5B  in BEC were correlated with asthma, asthma exacerbations, and T2 biomarkers ( P  &lt; 0.01). SNPs associated with asthma and IIPs in previous GWASs were eQTL SNPs for  MUC5AC ,  MUC5B , or  TOLLIP , however, they were not in strong linkage disequilibrium. The risk alleles for asthma or protective alleles for IIPs were associated with higher expression of  MUC5AC  and lower expression of  MUC5B . rs11603634, rs12788104, and rs28415845 associated with moderate-to-severe asthma or adult onset asthma in previous GWASs were not associated with asthma severity ( P  &gt; 0.8). SNPs associated with asthma in chr11p15.5 region are not associated with asthma severity neither with IIPs. Higher expression of  MUC5AC  and lower expression of  MUC5B  are risk for asthma but protective for IIPs.

Genetic analyses of chr11p15.5 region identify MUC5AC - MUC5B associated with asthma-related phenotypes