Volume 89, Issue 1
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Interferon-γ (IFN-γ) is a key cytokine in the immune response to (Mtb). Many studies established IFN-γ responses are influenced by host genetics, however differed widely by the study design and heritability estimation method. We estimated heritability of IFN-γ responses to Mtb culture filtrate (CF), ESAT-6, and Antigen 85B (Ag85B) in 1,104 Ugandans from a household contact study. Our method separately evaluates shared environmental and genetic variance, therefore heritability estimates were not upwardly biased, ranging from 11.6% for Ag85B to 22.9% for CF. Subset analyses of individuals with latent Mtb infection or without human immunodeficiency virus infection yielded higher heritability estimates, suggesting 10–30% of variation in IFN-γ is caused by a shared environment. Immunosuppression does not negate the role of genetics on IFN-γ response. These estimates are remarkably close to those reported for components of the innate immune response. These findings have implications for the interpretation of IFN-γ response assays and vaccine studies.


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Supplementary PDF

  • Received : 31 Oct 2012
  • Accepted : 18 Dec 2012
  • Published online : 10 Jul 2013

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