Heritability analysis of cytokines as intermediate phenotypes of tuberculosis

Academic Article

Abstract

  • Numerous studies have provided support for genetic susceptibility to tuberculosis (TB); however, heterogeneity in disease expression has hampered previous genetic studies. The purpose of this work was to investigate possible intermediate phenotypes for TB. A set of cytokine profiles, including antigen-stimulated whole-blood assays for interferon (IFN)-γ, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, and the ratio of IFN to TNF, were analyzed in 177 pedigrees from a community in Uganda with a high prevalence of TB. The heritability of these variables was estimated after adjustment for covariates, and TNF-α, in particular, had an estimated heritability of 68%. A principal component analysis of IFN-γ, TNF-α, and TGF-β reflected the immunologic model of TB. In this analysis, the first component explained >38% of the variation in the data. This analysis illustrates the value of such intermediate phenotypes in mapping susceptibility loci for TB and demonstrates that this area deserves further research.
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Stein CM; Guwatudde D; Nakakeeto M; Peters P; Elston RC; Tiwari HK; Mugerwa R; Whalen CC
  • Start Page

  • 1679
  • End Page

  • 1685
  • Volume

  • 187
  • Issue

  • 11