A striking feature of TB is that only 10% of infected individuals develop the disease. While a significant proportion of inter-individual variation in susceptibility to TB can be attributed to environmental factors, a substantial portion is thought to be due to host genetic factors. Indeed, several lines of evidence indicate that genetic factors contribute to inter-individual differences in susceptibility to TB, including the observation that the rate of TB in monozygotic twins is more than two-times higher than that observed among dizygotic twins. In addition, multiple rare single-gene mutations with high penetrance have also been linked with susceptibility to mycobacteria. However, although genetic studies of TB have identified important pathways involved in protective immunity, very little is yet known about the underlying genetic determinants or mechanisms contributing to differences in susceptibility to TB at the population.
In close collaboration with Luis Barreiro (Sainte Justine Hospital, Montreal, Canada), Yoav Gilad (University of Chicago, USA) and Lluis Quintana-Murci (Institut Pasteur, Paris), we combine expertise in immunology, human and molecular genetics, and statistics, to identify genes and regulatory pathways that contribute to inter-individual variability in the immune response to infection with MTB.