RNA-seq of monocyte derived macrophages and dendritic cells in a Peruvian Tuberculosis cohort

In this study, we sought to analyze the effects of genetic variants on gene expression levels in relation to the history of infectious disease and cell type. To do this, we focused on a Peruvian human cohort that had been previously genotyped who either progressed to active tuberculosis (TB) disease (cases) or did not progress to TB (controls). We isolated monocytes from PBMC samples of these individuals and differentiated in vitro to dendritic cells (DCs) and macrophages (MPs). We performed RNA-seq for each sample using a modified Smart-seq protocol for low-input RNA-sequencing. We measured the impact of genetic variants on gene expression by identifying expression quantitative trait loci (eQTL). We identified cell-type-specific eQTL genes as well as five genes that showed an interaction between eQTL variants and TB progression status in dendritic cells. We found that the top eQTL interaction with disease history was associated with a gene involved in tyrosine catabolism. We re-recruited a subset of household contacts of index TB patients who had been infected with Mtb and either progressed to active TB disease (progressors, cases) or remained TB-disease-free until sampling (non-progressors, controls) after initial enrollment. We restricted the analysis to high-quality data from 63 progressors and 63 non-progressors, sampled a median of 6 years after exposure to TB in the household. We generated gene expression profiles using RNA-seq in monocyte-derived dendritic cells (118 samples) and macrophages (109 samples) from these previously genotyped participants to conduct an eQTL mapping study. *************************************************************** Submitter declares that raw data will be available through dbGaP ***************************************************************