Fig. 5: A FOXA3 asthma risk eQTL drives metaplastic mucus secretory gene expression. | Nature Communications

Fig. 5: A FOXA3 asthma risk eQTL drives metaplastic mucus secretory gene expression.

From: Nasal airway transcriptome-wide association study of asthma reveals genetically driven mucus pathobiology

Fig. 5

a Locuszoom plots of COA GWAS (top) and nasal FOXA3 eQTL analyses (bottom) at the FOXA3 gene locus in chromosome 19. b Box plots of FOXA3 normalized expression in the GALA II cohort stratified by T2 status and rs8103278 genotype. N; T2 low AA: 18; T2 low GA: 116; T2 low GG: 190; T2 high AA: 29; T2 high GA: 135; T2 high GG: 193. 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 Bar plots of the percentage GALA II subjects who are asthmatics among the different T2 status by rs8103278 genotype groups. Dashed line indicates the proportion of asthmatics in the full GALA II cohort. N; T2 low AA: 18; T2 low GA: 116; T2 low GG: 190; T2 high AA: 29; T2 high GA: 135; T2 high GG: 193. d Volcano plot of FOXA3 (rs8103278) genome-wide trans-eQTL gene analysis. LFC estimate of each gene is obtained from limma by regressing gene expression values on additively coded rs8103278 genotype (A/A: 0; G/A: 1; G/G: 2). Genes with LFC > 0.1 and p value (two-sided) < 0.05 are highlighted. e Test for enrichment of WGCNA nasal epithelium gene co-expression network (previously identified) genes within FOXA3 trans-eQTL gene set. The −log10 p values for enrichment of network genes within the set of FOXA3 trans-eQTL genes (black) and MUC5AC trans-eQTL genes (gray) are shown with bars. Top network genes and select pathways and cell types enriched among network genes are shown. Enrichment p values were obtained from a one-sided hypergeometric test. f Genomic location of FOXA3 eQTL variant (rs8103278) and its colocalization with a ELF1 binding site and cross-species conserved region. g ELF1 core binding motif containing the rs8103278 variant. Nucleotide information content is indicated by the size of nucleotide letter abbreviation. The nucleotide in the red box is the rs8103278 SNP site. This high information content position assumes the high-expressing rs8103278 G nucleotide 96.7% of the time, while the alternate rs8103278 A allele is not present.

Back to article page