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

• Published in: The Journal of asthma Vol. 60; no. 10; p. 1824
• Main Authors: Li, Xingnan, Li, Huashi, Christenson, Stephanie A, Castro, Mario, Denlinger, Loren C, Erzurum, Serpil C, Fahy, John V, Gaston, Benjamin M, Israel, Elliot, Jarjour, Nizar N, Levy, Bruce D, Mauger, David T, Moore, Wendy C, Zein, Joe, Kaminski, Naftali, Wenzel, Sally E, Woodruff, Prescott G, Bleecker, Eugene R, Meyers, Deborah A
• Format: Journal Article
• Language: English
• Published: England 03.10.2023
• Subjects: Asthma - genetics; Cross-Sectional Studies; Genome-Wide Association Study; Humans; Mucin 5AC - genetics; Mucin-5B - genetics; Phenotype; RNA, Messenger; genetic association; eQTL; MUC5B; Asthma susceptibility; MUC5AC; asthma severity; gene expression
• ISSN: 1532-4303
• DOI: 10.1080/02770903.2023.2193631

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 ( , , , , , and ) and asthma phenotypes were performed in the longitudinal cohort (  = 156) with RNAseq in BEC, and replicated in the cross-sectional cohort (  = 155). eQTL (  = 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 and and lower expression of in BEC were correlated with asthma, asthma exacerbations, and T2 biomarkers (  < 0.01). SNPs associated with asthma and IIPs in previous GWASs were eQTL SNPs for , , or , however, they were not in strong linkage disequilibrium. The risk alleles for asthma or protective alleles for IIPs were associated with higher expression of and lower expression of . rs11603634, rs12788104, and rs28415845 associated with moderate-to-severe asthma or adult onset asthma in previous GWASs were not associated with asthma severity (  > 0.8). SNPs associated with asthma in chr11p15.5 region are not associated with asthma severity neither with IIPs. Higher expression of and lower expression of are risk for asthma but protective for IIPs.