Chandelier
Senior Member (Voting Rights)
Tissue-resident immune cells drive genetic risk in autoimmune and lung diseases
Abstract
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).
Web | DOI | PDF | Nature Immunology | Open Access
Schmiedel, Benjamin J.; Gonzalez-Colin, Cristian; Fajardo-Rosas, Vicente; Rocha, Job; Simon, Hayley; Ottensmeier, Johannes; Ramírez-Bernabé, Ignacio E.; Cano, April; De la Cruz Castillo, Angel; Márquez-Gómez, Elizabeth; Ha, Brendan; Greenbaum, Jason A.; Chudley, Lindsey; Cave, Judith; Alzetani, Aiman; Woo, Edwin; Shackcloth, Michael; Chee, Serena J.; Chandra, Vivek; Kronenberg, Mitchell; Peters, Bjoern; Ottensmeier, Christian H.; Ganesan, Anusha-Preethi; Vijayanand, Pandurangan
Abstract
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).
Web | DOI | PDF | Nature Immunology | Open Access