Fig. 3: Functional annotation of pleiotropic genes across 14 lung-gastrointestinal trait pairs.

The heatmaps display functional annotations on the x-axis and 14 lung-gastrointestinal trait pairs on the y-axis, with significant cells filled in colour. The bars represented the number of trait pairs for each annotation item and the number of significant annotation items for each trait pair, respectively. Significantly enriched items were determined with Bonferroni-corrected P ≤ 0.05 for GSEA [normalised enrichment score > 2, GO terms and KEGG terms], TSEA, and CSEA, as well as FDR-corrected P ≤ 0.05 for TWAS and PWAS. All annotations were evaluated against a two-sided alternative hypothesis. GO and KEGG pathway enrichment analyses revealed that 24 unique biological processes related to immune or inflammatory response related activities were enriched (see also Supplementary Data 12). TSEA using the deTS method revealed 5 significantly enriched tissues (see also Supplementary Data 13). The top 5 enriched immune cell types from CSEA calculated by WebCSEA are shown (see also Supplementary Data 14). TWAS and PWAS were performed using FUSION based on 49 normal tissues from GTEx V8 and the plasma proteome built from the ARIC study, respectively (see also Supplementary Data 16-17). GO: Gene Ontology. KEGG: Kyoto Encyclopedia of Genes and Genomes. GSEA: gene set enrichment analysis. TSEA: tissue-specific enrichment analysis. CSEA: cell-type specific enrichment analysis. TWAS: transcriptome-wide association study. PWAS: proteome-wide association study. GTEx: Genotype-Tissue Expression project. CP: colon polyp. DD: diverticular disease. GORD: gastro-oesophageal reflux disease. IBS: irritable bowel syndrome. CB: chronic bronchitis. PUD: peptic ulcer disease. LUSC: lung squamous cell carcinoma. CRC: colorectal cancer. Source data were provided as a Source Data file.