Fig. 5

Genotype background influences lung cancer risk. a Combined environmental and genetic effect on the expression of the FXYD5 gene in nasal tissues. For each nasal sample, we present the expression level of the gene FXYD5 separately for never (pink), former (green) and current (blue) smokers. Samples are further stratified depending on the genotype of the subject at the 19:35660670:G:A locus (Ref/Ref: homozygous reference; Ref/Alt: heterozygous; Alt/Alt homozygous Alternative). The p-value gives the significance level of an interaction effect of the smoking status and the genotype at 19:35660670:G:A on the expression of the FXYD5 gene (see the ‘Methods’ section). GWAS enrichment analysis: (b) Network representation of the 4 bronchial regulons enriched in GWAS genes. The 4 TFs are shown as squares and their target genes in the bronchial network as circles. The colour of the nodes indicates whether the gene/TF is a smoke injury risk gene (blue), a gene that co-localizes with a GWAS hit (i.e. no threshold on eQTL significance) (red) or both (green). The level of overrepresentation for genes in the network of those TFs can be found in Table 1. c Activity level of each of the 4 TFs in nasal tissue, depending on the disease status of the patient (green, healthy volunteer; orange, clinic patient without cancer; purple, clinic patient with cancer). Stars represent the significance of a two-sample t-test (ns, p > 0.05; *p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001; ****p ≤ 0.0001)