Stein, Catherine M.Guwatudde, DavidNakakeeto, MargaretPeters, PierreElston, Robert C.Tiwari, Hemant K.Mugerwa, RoyWhalen, Christopher C.2022-04-292022-04-292003Stein, C. M., Guwatudde, D., Nakakeeto, M., Peters, P., Elston, R. C., Tiwari, H. K., ... & Whalen, C. C. (2003). Heritability analysis of cytokines as intermediate phenotypes of tuberculosis. The Journal of infectious diseases, 187(11), 1679-1685.https://academic.oup.com/jid/article-abstract/187/11/1679/884405https://nru.uncst.go.ug/handle/123456789/3003Numerous 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)–g, tumor necrosis factor (TNF)–a, transforming growth factor (TGF)–b, 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-a, in particular, had an estimated heritability of 68%. A principal component analysis of IFN-g, TNF-a, and TGF-b reflected the immunologic model of TB. In this analysis, the first component explained 138% 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.enHeritability AnalysisCytokinesPhenotypesTuberculosisArticle