Fig. 4

Association of long-term abnormal methylation within HPA-axis genes in former PICU patients with impaired long-term developmental outcomes. This heatmap summarises the results of the multivariable linear regression analyses assessing associations between abnormal methylation within HPA-axis genes 2 years after critical illness and developmental outcomes of former PICU patients evaluated at that time (n = 713), adjusted for baseline risk factors and technical variation. Each box shows the percentage of the 100 iterations for which the p values across the 10 test folds (computed with Fisher’s method [51]) are significant (p < 0.05) for a given CpG site (X axis) and outcome (Y axis). Darker colour intensity indicates a larger percentage of iterations being significant. For each CpG site, the location within the respective gene is also indicated (due to multiple splice variants, multiple gene locations are possible). The labels within the boxes indicate whether the observed abnormal methylation correlates with a better score for the long-term outcome (benefit ‘B’), or with a worse score (harm ‘H’). Abbreviations: IQ: intelligence quotient, SD: standard deviation, UTR: untranslated region, VMI: visual motor integration