Systems genetics of the nuclear factor-κB signal transduction network. I. Detection of several quantitative trait loci potentially relevant to aging

Vincent P. Diego, Joanne E. Curran, Jac Charlesworth, Juan M. Peralta, V. Saroja Voruganti, Shelley A. Cole, Thomas D. Dyer, Matthew P. Johnson, Eric K. Moses, Harald H.H. Göring, Jeff T. Williams, Anthony G. Comuzzie, Laura Almasy, John Blangero, Sarah Williams-Blangero

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    1 Scopus citations

    Abstract

    A theory of aging holds that senescence is caused by a dysregulated nuclear factor kappa B (NF-κB) signal transduction network (STN). We adopted a systems genetics approach in our study of the NF-κB STN. Ingenuity Pathways Analysis (IPA) was used to identify gene/gene product interactions between NF-κB and the genes in our transcriptional profiling array. Principal components factor analysis (PCFA) was performed on a sub-network of 19 genes, including two initiators of the toll-like receptor (TLR) pathway, myeloid differentiation primary response gene (88) (MyD88) and TIR (Toll/interleukin-1 receptor)-domain-containing adapter-inducing interferon-β (TRIF). TLR pathways are either MyD88-dependent or TRIF-dependent. Therefore, we also performed PCFA on a subset excluding the MyD88 transcript, and on another subset excluding two TRIF transcripts. Using linkage analysis we found that each set gave rise to at least one factor with a logarithm of the odds (LOD) score greater than 3, two on chromosome 15 at 15q12 and 15q22.2, and another two on chromosome 17 at 17p13.3 and 17q25.3. We also found several suggestive signals (2 < LOD score < 3) at 1q32.1, 1q41, 2q34, 3q23, and 7p15.3. We are currently examining potential associations with single nucleotide polymorphisms within the 1-LOD intervals of our linkage signals.

    Original languageEnglish (US)
    Pages (from-to)11-19
    Number of pages9
    JournalMechanisms of Ageing and Development
    Volume133
    Issue number1
    DOIs
    StatePublished - Jan 2012

    Keywords

    • Gene expression network
    • Linkage analysis
    • Nuclear factor kappa B
    • Principal components factor analysis
    • Systems genetics

    ASJC Scopus subject areas

    • Aging
    • Developmental Biology

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