Background: The phases of human growth are associated with gene expression (GE) changes1, raising the possibility that rhythmic patterns of GE occur throughout childhood.
Objective: In this study, we have assessed time-series patterns of GE profiles associated with age to characterise oscillations.
Methods: GE analysis was conducted on cells of lymphoid origin from normal individuals through childhood (n=87, 43 males and 44 females, range 2 months29 years)1. Clustered patterns of GE time-series were identified by STEM (short timeseries expression miner)2 and confirmed using unsupervised multidimensional scaling (MDS) (Qlucore Omics Explorer 3.0). Statistically associated GE was assessed using ANOVA (P<1×10−4). Associated causal networks associated with GE were identified algorithmically (Ingenuity Pathway Analysis).
Results: Gender associated groups of gene probe (GP) set profiles were identified with oscillations of gene expression; 487 GP sets in males and 3302 in females with an overlap of 145. MDS and time-series analysis identified two underlying patterns of GE (i and ii), the first (i) with peaks at 5.0, 7.2 and 12.1 years (99 GP-sets) and the second (ii) with peaks at 5.6 and 10.2 years (388 GP-sets) in males; similar oscillations were seen in females with (i) peaks at 5.0, 7.0 and 11.3 years (1221 GP-sets) and (ii) 3.7 and 7.0 years (2081 GP-sets). Causal network analysis on these GE profiles in both sexes implicated metabolic processes (P<1.3×10−3) with specific differences in the second pattern of oscillation (ii) in GE between males and females in lipid and amino acid metabolism (both P<0.017). The overlap in GE between the sexes was associated with growth (P<1.3×10−5) causally linked to GH and IGF1 action.
Conclusion: This study has identified gender specific variations in age-related GE oscillations associated with human growth and development that highlight gender-specific differences in metabolism and emphasise the role of the GH/IGF1 axis.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology