Fig. 1: Overview of the study design.

a Summary of the comprehensive pleiotropic analyses from different perspectives for multiple lung and gastrointestinal diseases in individuals of European, East Asian, and African ancestry. The genetic correlations at the global and local levels in each population were firstly examined. Created in BioRender. You, D. (2025) https://BioRender.com/j53h646. b Cross-trait meta-analysis and gene-based analyses were conducted to identify causal pleiotropic variants and genes. The functional annotation, TWAS, PWAS, and gene-environment interaction analyses were subsequently performed to explore biological functions. c Bi-directional MR and mediation analyses were performed to identify putative causal relationships and further clarify the shared biological mechanism between lung and gastrointestinal diseases. Created in BioRender. You, D. (2025) https://BioRender.com/j53h646. EUR: European. EAS: East Asian. AFR: African. AB: acute bronchitis. CB: chronic bronchitis. COPD: chronic obstructive pulmonary disease. FEV1: forced expiratory volume in 1 s. FVC: forced vital capacity. FEV1/FVC: FEV1/FVC ratio. PEF: peak expiratory flow. ILD: interstitial lung disease. IPF: idiopathic pulmonary fibrosis. LUAD: lung adenocarcinoma. LUSC: lung squamous cell carcinoma. SCLC: small cell lung carcinoma. LCES: lung cancer in ever smokers. LCNS: lung cancer in never smokers. Bact-pneumo: bacterial pneumoniae. Viral-pneumo: viral pneumonia. CP: colon polyp. CRC: colorectal cancer. DD: diverticular disease. GORD: gastro-oesophageal reflux disease. IBD: inflammatory bowel disease. CD: Crohn’s disease. UC: ulcerative colitis. IBS: irritable bowel syndrome. PUD: peptic ulcer disease. TWAS: transcriptome-wide association study. PWAS: proteome-wide association study. SNP: single-nucleotide polymorphism. MR: Mendelian randomisation. IV: instrumental variable.