# Genetic determinants of inter-individual variation in the dynamic transcriptional innate immune response to Mycobacterium tuberculosis

> **NIH NIH F31** · UNIVERSITY OF CHICAGO · 2022 · $46,726

## Abstract

PROJECT SUMMARY
Infectious diseases are a major public health burden throughout the world. Tuberculosis (TB), caused by the
pathogen Mycobacterium tuberculosis (Mtb), is estimated to kill nearly 2 million individuals worldwide every year
alone. Notably, humans show remarkable differences in susceptibility to many pathogens, including Mtb.
Arguably, this heterogeneity arises from variation in the immune response, which is responsible for preventing
and controlling infection. Although a significant proportion of inter-individual variation in susceptibility to Mtb
infection can be attributed to environmental factors, a substantial portion is due to host genetic factors. The
importance of host genetic factors in susceptibility to clinical TB has been demonstrated by twin and family
studies. However, the underlying genetic factors that drive inter-individual differences in susceptibility to Mtb
infection remain largely unknown, especially at the population level. Using combined expertise in functional
genomics, computational biology, human immunology, and population genetics, I propose to: (i)
characterize the
inter-individual and inter-population transcriptional variation in the innate immune response to Mtb infection; (ii)
map expression quantitative trait loci (eQTLs) that are associated with variation in the response to Mtb infection ;
and (iii) determine the role of recent positive selection in shaping ancestry-associated differences in gene
expression. This work will yield unprecedented insight into the genetic determinants underlying inter-individual
and population-associated variation in the transcriptional innate immune response to Mtb infection. Further,
these efforts will establish innovative, novel, and empirically-grounded transcriptional profiling strategies to
pinpoint highly-promising genetic candidates for Mtb susceptibility, which will allow us to identify the individuals
who are at increased risk for TB, one of the greatest health burdens facing modern human populations.

## Key facts

- **NIH application ID:** 10543035
- **Project number:** 5F31HL156419-02
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Haley Elizabeth Randolph
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,726
- **Award type:** 5
- **Project period:** 2021-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10543035

## Citation

> US National Institutes of Health, RePORTER application 10543035, Genetic determinants of inter-individual variation in the dynamic transcriptional innate immune response to Mycobacterium tuberculosis (5F31HL156419-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10543035. Licensed CC0.

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