ArticlePLoS genetics2017
Deciphering the genetic control of gene expression following Mycobacterium leprae antigen stimulation.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Factors associated with the development of leprosy in Brazilian contacts: a systematic review.Revista do Instituto de Medicina Tropical de Sao Paulo · 2022Pooled it
- Functional single nucleotide polymorphisms in CACNA2D3 and other autophagy-related genes are associated with leprosy among Brazilians.PLoS neglected tropical diseases · 2026Article
- Host genotypes interact with microbial communities to modulate gene expression in the human intestine.medRxiv : the preprint server for health sciences · 2026Article
- Genotype × environment interactions in gene regulation and complex traits.Nature genetics · 2024Review
- Characterization of caffeine response regulatory variants in vascular endothelial cells.eLife · 2024Article
- Genome-wide meta-analysis and fine-mapping prioritize potential causal variants and genes related to leprosy.MedComm · 2023Article
- Genetic control of the dynamic transcriptional response to immune stimuli and glucocorticoids at single-cell resolution.Genome research · 2023Article
- Analysis of transcriptional changes in the immune system associated with pubertal development in a longitudinal cohort of children with asthma.Nature communications · 2023Article
- Article
- Genetic control of the dynamic transcriptional response to immune stimuli and glucocorticoids at single cell resolution.bioRxiv : the preprint server for biology · 2022Article
- Genome-wide association study of leprosy in Malawi and Mali.PLoS pathogens · 2022Article
- Gene expression patterns associated with multidrug therapy in multibacillary leprosy.Frontiers in cellular and infection microbiology · 2022Article
- A signature of Neanderthal introgression on molecular mechanisms of environmental responses.PLoS genetics · 2021Article
- Article
- Reduction of host cell mitochondrial activity as Mycobacterium leprae's strategy to evade host innate immunity.Immunological reviews · 2021Review
- Dynamic effects of genetic variation on gene expression revealed following hypoxic stress in cardiomyocytes.eLife · 2021Article
- Transcriptomic Analysis ofFrontiers in cellular and infection microbiology · 2021Article
- Large-Scale Gene Expression Signatures Reveal a Microbicidal Pattern of Activation inFrontiers in immunology · 2021Article
- Polymorphisms in mitochondrial ribosomal protein S5 (MRPS5) are associated with leprosy risk in Chinese.PLoS neglected tropical diseases · 2020Article
- Mycolactone toxin induces an inflammatory response by targeting the IL-1β pathway: Mechanistic insight into Buruli ulcer pathophysiology.PLoS pathogens · 2020Article
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Leprosy is a human infectious disease caused by Mycobacterium leprae. A strong host genetic contribution to leprosy susceptibility is well established. However, the modulation of the transcriptional response to infection and the mechanism(s) of disease control are poorly understood. To address this gap in knowledge of leprosy pathogenicity, we conducted a genome-wide search for expression quantitative trait loci (eQTL) that are associated with transcript variation before and after stimulation with M. leprae sonicate in whole blood cells. We show that M. leprae antigen stimulation mainly triggered the upregulation of immune related genes and that a substantial proportion of the differential gene expression is genetically controlled. Indeed, using stringent criteria, we identified 318 genes displaying cis-eQTL at an FDR of 0.01, including 66 genes displaying response-eQTL (reQTL), i.e. cis-eQTL that showed significant evidence for interaction with the M. leprae stimulus. Such reQTL correspond to regulatory variations that affect the interaction between human whole blood cells and M. leprae sonicate and, thus, likely between the human host and M. leprae bacilli. We found that reQTL were significantly enriched among binding sites of transcription factors that are activated in response to infection, and that they were enriched among single nucleotide polymorphisms (SNPs) associated with susceptibility to leprosy per se and Type-I Reaction, and seven of them have been targeted by recent positive selection. Our study suggested that natural selection shaped our genomic diversity to face pathogen exposure including M. leprae infection.
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