Higher native Peruvian genetic ancestry proportion is associated with tuberculosis progression risk

We investigated whether ancestry-specific genetic factors affect tuberculosis (TB) progression risk in a cohort of admixed Peruvians. We genotyped 2,105 patients with TB and 1,320 household contacts (HHCs) who were infected with Mycobacterium tuberculosis (M. tb) but did not develop TB and inferred each individ-ual's proportion of native Peruvian genetic ancestry. Our HHC study design and our data on potential con-founders allowed us to demonstrate increased risk independent of socioeconomic factors. A 10% increase in individual-level native Peruvian genetic ancestry proportion corresponded to a 25% increased TB progres-sion risk. This corresponds to a 3-fold increased risk for individuals in the highest decile of native Peruvian genetic ancestry versus the lowest decile, making native Peruvian genetic ancestry comparable in effect to clinical factors such as diabetes. Our results suggest that genetic ancestry is a major contributor to TB pro-gression risk and highlight the value of including diverse populations in host genetic studies.