Tissue-resident immune cells drive genetic risk in autoimmune and lung diseases

Common genetic variants are associated with risk of lung and autoimmune diseases. However, we have a limited understanding of the pathological effects of these disease variants, specifically in tissue-resident immune cells at the frontier of infection and disease in the lung. To address this, we performed single-cell expression quantitative trait locus (eQTL) analysis across 29 distinct immune cell subsets isolated from lung tissue. Colocalization analysis of lung immune cell eQTLs with genome-wide association study (GWAS) signals from lung diseases, and infectious and autoimmune diseases, implicate disease-associated variants and their target genes functioning in a single or restricted group of cell types. Several genes, including ZFP57, showed significant colocalization between lung immune cell eQTLs and GWAS signals from multiple systemic and organ-restricted autoimmune diseases, highlighting shared genetic mechanisms underlying the risk of disease. Overall, our study shows that disease-associated variants from a wide range of autoimmune diseases impact gene expression in tissue-resident immune cell types ( https://lung.dice-database.org ).