To determine whether increased transcription of immune activation genes in high-lonely individuals might stem from increased activity of the pro-inflammatory NF-κB transcription control pathway, TELiS bioinformatics analyses also assessed the relative distribution of NF-κB/Rel response elements in differentially expressing promoters. Results showed a 2.9-fold greater prevalence of NF-κB/Rel motifs among promoters of genes over-expressed in socially isolated individuals relative to those over-expressed in socially integrated individuals (TRANSFAC V$CREL_01 motif: average 0.129 ± standard error 0.040 sites/promoter for genes over-expressed in socially integrated individuals versus 0.377 ± 0.086 in isolated; difference p = 0.0108 by t-test) (Figure 2). Similar results emerged in parametric sensitivity analyses, with an average 2.69-fold (± 0.47) difference across all 9 parametric combinations of promoter length and motif match stringency (p = 0.0069), and an average 1.30-fold (± 0.09) difference in analyses utilizing 5% FDR stringency in gene selection (p < 0.0001).
