Investigating the role of gene-gene interactions in TB susceptibility

dc.contributor.authorDaya, Michelleen_ZA
dc.contributor.authorVan der Merwe, Lizeen_ZA
dc.contributor.authorVan Helden, Paul D.en_ZA
dc.contributor.authorMoller, Marloen_ZA
dc.contributor.authorHoal, Eileen G.en_ZA
dc.descriptionCITATION: Daya, M. et al. 2015. Investigating the role of gene-gene interactions in TB susceptibility. PLoS ONE, 10(4): 1-25, doi: 10.1371/journal.pone.0123970.en_ZA
dc.descriptionThe original publication is available at
dc.descriptionPublication of this article was funded by the Stellenbosch University Open Access Fund.
dc.description.abstractTuberculosis (TB) is the second leading cause of mortality from infectious disease worldwide. One of the factors involved in developing disease is the genetics of the host, yet the field of TB susceptibility genetics has not yielded the answers that were expected. A commonly posited explanation for the missing heritability of complex disease is gene-gene interactions, also referred to as epistasis. In this study we investigate the role of gene-gene interactions in genetic susceptibility to TB using a cohort recruited from a high TB incidence community from Cape Town, South Africa. Our discovery data set incorporates genotypes from a large a number of candidate gene studies as well as genome-wide data. After limiting our search space to pairs of putative TB susceptibility genes, as well as pairs of genes that have been curated in online databases as potential interactors, we use statistical modelling to identify pairs of interacting SNPs. We attempt to validate the top models identified in our discovery data set using an independent genome-wide TB case-control data set from The Gambia. A number of models were successfully validated, indicating that interplay between the NRG1 - NRG3, GRIK1 - GRIK3 and IL23R - ATG4C gene pairs may modify susceptibility to TB. Gene pairs involved in the NF-κB pathway were also identified in the discovery data set (SFTPD - NOD2, ISG15 - TLR8 and NLRC5 - IL12RB1), but could not be tested in the Gambian study group due to lack of overlapping data.en_ZA
dc.description.versionPublisher's version
dc.format.extent25 pages : illustrationsen_ZA
dc.identifier.citationDaya, M. et al. 2015. Investigating the role of gene-gene interactions in TB susceptibility. PLoS ONE, 10(4): 1-25 doi:10.1371/journal.pone.0123970.en_ZA
dc.identifier.issn1932-6203 (online)
dc.identifier.issn1932-6203 (print)
dc.identifier.otherdoi: 10.1371/journal.pone.0123970
dc.publisherPublic Library of Scienceen_ZA
dc.rights.holderAuthors retain copyrighten_ZA
dc.subjectTuberculosis (TB) susceptibility geneticsen_ZA
dc.subjectGene-gene interactionsen_ZA
dc.titleInvestigating the role of gene-gene interactions in TB susceptibilityen_ZA
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