Higher Native Peruvian ancestry proportion is associated with tuberculosis progression risk

The global burden of pulmonary tuberculosis (TB) remains a major public health problem that is particularly severe among and disproportionately affects indigenous populations. We aimed to investigate whether genetic factors related to indigeneity affect TB progression risk in a cohort of admixed Peruvians with active TB and their latently infected household contacts. Our results show that Native Peruvian ancestry is positively associated with TB progression risk: a 10% increase in native ancestry tracks with a 25% increased risk of TB progression. This risk is independent of the potentially confounding socio-demographic and environmental factors that we tested here. Our results demonstrate that the genetic contribution to TB risk varies among populations and brings new insight to the long-standing debate on the role of genetic ancestry in susceptibility to TB. Additionally, our study highlights the value of including diverse populations in genetic studies of infectious diseases and other complex phenotypes, and provides a road map for future similar studies where it is important to account for confounding non-genetic risk factors to identify genetic risk factors.