Fig. 1: Schematic visualization of the study workflow.
From: An atlas of the shared genetic architecture between atopic and gastrointestinal diseases
The genetic correlations between 10 traits of ADs and 11 GIDs were first determined on both genome-wide level and genomic regional level by LDSC and LAVA, respectively. The subsequent analysis was conducted based on two hypotheses. (1) To detect if the shared genetic architecture between ADs and GIDs were converged on common cellular pathways, comorbidity-associated genes were prioritized using SMR in bulk-eQTLs data of nine tissues and sc-eQTL data from PBMC. Comorbidity-associated cell types were projected to single-cell RNAseq data from blood, gut, lung and airway tissues. Then the druggability of the prioritized genes were assessed in public drug databases. (2) To investigate the directional causality between AD-GID which might partially explain the comorbidities, multiple bi-directional MR approaches were incorporated, followed by a variety of sensitivity analysis. AD, atopic disease. GID, gastrointestinal diseases. LDSC, linkage disequilibrium score regression. LAVA, local analysis of [co]variant association. sc-eQTL, single cell expression quantitative trait loci. SMR, summary-data-based Mendelian Randomization. PBMC, peripheral blood mononuclear cells. COA, child-onset asthma. AOA, adult-onset asthma. MtoS asthma, Moderate-to-severe asthma. CD, Crohn’s disease. CRC, colorectal carcinoma. GERD, gastroesophageal reflux disease. UC, ulcerative colitis. IBS, irritable bowel syndrome. Created in BioRender. Hu, S. (2024) https://BioRender.com/q95x753.
