Fig. 4: A MUC5AC asthma risk eQTL exerts trans-effects on mucus secretory cell genes.

a Locuszoom plots of AOA GWAS (top) and nasal MUC5AC eQTL analyses (bottom) at the gel forming mucin locus on chromosome 11. GWAS p values were obtained from two-sided tests. b Box plots of normalized MUC5AC expression in the GALA II cohort stratified by T2 status and rs12788104 genotype. N; T2 low AA: 67; T2 low GA: 166; T2 low GG: 91; T2 high AA: 77; T2 high GA: 180; T2 high GG: 100. Box centers give the median, upper and lower box bounds correspond to first and third quartiles, and the upper/lower whiskers extend from the upper/lower bounds up to/down from the largest/smallest value, no further than 1.5× IQR from the upper/lower bound (where IQR is the inter-quartile range). Data beyond the end of whiskers are plotted individually. c Representative images of MUC5AC IF staining (red) among in vitro ALI nasal airway epithelial cultures from rs12788104 A/A (n = 4 donors, 8–11 field of views per donor; left) and G/G (n = 4 donors, 8–11 field of views per donor; right) genotype donors. Nuclei were counterstained with DAPI (blue). Scale bars: 50 μm. All images were captured on the Echo Revolve R4 and for each image, brightness and contrasts were uniformly adjusted relative to the brightest feature to balance exposure of each color channel. d Box plots of MUC5AC + mean cell counts (left) and secreted MUC5AC mean protein levels (right) between rs12788104 A/A (n = 5 donors, 6 technical replicates per donor for MUC5AC protein; n = 4 donors, 8–11 field of views per donor for MUC5AC + cell counts) and G/G genotype groups (n = 5 donors, 6 technical replicates per donor for MUC5AC protein; n = 4 donors, 8–11 field of views per donor for MUC5AC + cell counts). P values were obtained from two-sided tests. For MUC5AC + cell count data (left), p value was obtained from GLMMTMB. For the MUC5AC protein levels data (right), p value was provided via Satterthwaite’s degrees of freedom method implemented in R package lmerTest. Box centers give the median, upper and lower box bounds correspond to first and third quartiles, and the upper/lower whiskers extend from the upper/lower bounds up to/down from the largest/smallest value, no further than 1.5× IQR from the upper/lower bound (where IQR is the inter-quartile range). Data beyond the end of whiskers are plotted individually. e Gene correlation network of MUC5AC trans-eQTL genes which are enriched among mucus biology-related pathways or among mucus secretory cells. Edges are drawn between each gene and its ten highest correlated genes. Edge thickness: Pearson correlation. Node color: enrichment term. Node size: trans-eQTL LFC estimate. Asterisk next to a node indicates trans-eQTL gene with FDR < 0.05.