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

Area of Science:

• Genetics
• Infectious Diseases
• Population Health

Background:

• Tuberculosis (TB) remains a global health challenge, with progression from infection to active disease varying significantly among individuals.
• Host genetic factors are suspected to influence TB susceptibility and progression, but their specific contributions in admixed populations are not well understood.

Purpose of the Study:

• To investigate the role of ancestry-specific genetic factors in determining tuberculosis (TB) progression risk within a Peruvian cohort.
• To quantify the association between native Peruvian genetic ancestry and the risk of developing active TB after infection with Mycobacterium tuberculosis.

Main Methods:

• Genotyping of 2,105 TB patients and 1,320 infected household contacts (HHCs) from Peru.
• Inference of individual-level native Peruvian genetic ancestry proportions.
• Statistical analysis accounting for potential confounders and utilizing the HHC study design to isolate genetic effects.

Main Results:

• A 10% increase in native Peruvian genetic ancestry was associated with a 25% higher risk of TB progression.
• Individuals in the highest decile of native Peruvian ancestry faced a 3-fold increased risk compared to those in the lowest decile.
• The effect of genetic ancestry on TB progression risk was found to be independent of socioeconomic factors and comparable to clinical risk factors like diabetes.

Conclusions:

• Genetic ancestry is a significant determinant of tuberculosis progression risk in admixed Peruvian populations.
• Host genetic factors, particularly those linked to native Peruvian ancestry, play a crucial role in TB pathogenesis.
• These findings underscore the importance of including diverse populations in host genetic studies to fully understand TB.