Demographic and genetic factors influence the abundance of infiltrating immune cells in human tissues.

TitleDemographic and genetic factors influence the abundance of infiltrating immune cells in human tissues.
Publication TypeJournal Article
Year of Publication2020
AuthorsMarderstein AR, Uppal M, Verma A, Bhinder B, Tayyebi Z, Mezey J, Clark AG, Elemento O
JournalNat Commun
Date Published2020 05 05
KeywordsAdult, 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

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.

Alternate JournalNat Commun
PubMed ID32371927
PubMed Central IDPMC7200670
Grant ListR01 CA194547 / CA / NCI NIH HHS / United States
UL1 TR002384 / TR / NCATS NIH HHS / United States
T32 GM083937 / GM / NIGMS NIH HHS / United States