Genetic control of the transcriptional response to active tuberculosis disease and treatment
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Understanding the functional impact of genomic sequence variants is critical for evaluating the role of genetic variation in the host response during tuberculosis (TB) disease and anti-TB treatment (ATT). Hitherto, there have been no genome-wide in vivo response expression quantitative trait loci (reQTL) studies conducted for active TB and ATT. Here, using longitudinal peripheral blood RNA-seq data from n = 48 patients with active TB who underwent ATT, we call sequence variants directly from these transcriptomes and impute them with a multi-ancestry reference panel. Associating our variants with the expression of nearby genes, we characterise thousands of cis-eQTL and hundreds of reQTL. We further show significant changes in cell type proportions during ATT through deconvolution of the bulk RNA-seq data and identify the putative cell type specific nature of cis-eQTL. Our work sheds light on the immunogenetics of TB disease and treatment, while providing a framework for studies using only RNA-seq data.
