Title | Demographic and genetic factors influence the abundance of infiltrating immune cells in human tissues. |
Publication Type | Journal Article |
Year of Publication | 2020 |
Authors | Marderstein AR, Uppal M, Verma A, Bhinder B, Tayyebi Z, Mezey J, Clark AG, Elemento O |
Journal | Nat Commun |
Volume | 11 |
Issue | 1 |
Pagination | 2213 |
Date Published | 2020 05 05 |
ISSN | 2041-1723 |
Keywords | Adult, Algorithms, Female, Gene Expression Profiling, Gene Regulatory Networks, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Immune System, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, T-Lymphocytes, Helper-Inducer, Thyroid Gland |
Abstract | Despite infiltrating immune cells having an essential function in human disease and patients' responses to treatments, mechanisms influencing variability in infiltration patterns remain unclear. Here, using bulk RNA-seq data from 46 tissues in the Genotype-Tissue Expression project, we apply cell-type deconvolution algorithms to evaluate the immune landscape across the healthy human body. We discover that 49 of 189 infiltration-related phenotypes are associated with either age or sex (FDR < 0.1). Genetic analyses further show that 31 infiltration-related phenotypes have genome-wide significant associations (iQTLs) (P < 5.0 × 10), with a significant enrichment of same-tissue expression quantitative trait loci in suggested iQTLs (P < 10). Furthermore, we find an association between helper T cell content in thyroid tissue and a COMMD3/DNAJC1 regulatory variant (P = 7.5 × 10), which is associated with thyroiditis in other cohorts. Together, our results identify key factors influencing inter-individual variability of immune infiltration, to provide insights on potential therapeutic targets. |
DOI | 10.1038/s41467-020-16097-9 |
Alternate Journal | Nat Commun |
PubMed ID | 32371927 |
PubMed Central ID | PMC7200670 |
Grant List | R01 CA194547 / CA / NCI NIH HHS / United States UL1 TR002384 / TR / NCATS NIH HHS / United States T32 GM083937 / GM / NIGMS NIH HHS / United States |