Description of datasets.

<p>For this study, three datasets were used; schizophrenia cases and controls, an antipsychotic-free set and a control dataset. Age and gender information is given for cases and controls separately. Gene expression data was generated in two batches (batch 1: Illumina H-8 and batch 2: Illumina H-12) and collected at different sites, information given in the fourth and fifth row). The batch effect resulting from the use of different arrays on different time points in the latter set was removed using the SampleNetwork R package <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0039498#pone.0039498-Oldham3" target="_blank">[62]</a>. The number of expressed genes is given in the last row. *DK  =  Denmark and NL  =  The Netherlands.</p

Visual representation of connections of genes in the Tan schizophrenia module.

<p>This figure shows target genes of the probes in the Tan schizophrenia module with the strongest connections only (<i>r</i> >0.64). Blue-colored nodes represent brain-expressed genes. Square-shape nodes indicate <i>cis</i>-regulation. Node size is related to the number of connections of that particular gene; a highly connected gene (i.e. ‘hub gene’) is therefore larger than genes with fewer connections. Red text indicates genes previously implicated in schizophrenia. Image created using Cytoscape software <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0039498#pone.0039498-Smoot1" target="_blank">[69]</a>.</p

Module eigengene significance for co-expression modules.

<p>The modules that were found by WGCNA in the first dataset are listed together with the number of genes they contain (shown in the second column). Differences in cases and controls were tested using a linear model with FDR correction. Results for the medicated cases versus controls are presented in column three and four. The modules that were found to be differentially expressed were also tested for significance between cases and controls in the antipsychotic-free set, and results are presented in the fifth and sixth column. The last column indicates the percentage of module content that was also found to be expressed in brain (log₂>4). For all genes in the other modules, this was found to be 45%. For the Tan module, this was significantly higher (Fisher <i>p</i> = 4.3×10⁻⁴).</p

Network construction identifies distinct modules of co-expressed genes.

<p>The network was constructed using gene expression data of 92 medicated schizophrenia cases and 78 controls (dataset 1). The dendrogram was produced by average linkage hierarchical clustering of genes using 1-topological overlap as dissimilarity measure (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0039498#s4" target="_blank">methods</a> section). Modules of co-expressed genes were assigned colors corresponding to the branches indicated by the horizontal bar beneath the dendrogram.</p

Amplitude of the best fitting models per metabolite with significance levels (in bold: Bonferroni-corrected significant results).

<p>T-statistic of the amplitudes, tmax (month during which levels peak), tmin (month during which levels are at their lowest), and best-fitting model based on deviance calculations. Feb = February; Nov = November; Sept = September; Dec = December.</p

Median concentrations of monoamine metabolites (in nmol/L) in cerebrospinal fluid with standard deviations (S.D.), per season (italics indicate totals).

<p>Median concentrations of monoamine metabolites (in nmol/L) in cerebrospinal fluid with standard deviations (S.D.), per season (italics indicate totals).</p

Median CSF 5-HAA Concentrations (in nmol/L) are plotted against Month of Birth.

<p>Bold line represents cosine, thin line represents LOESS and dashed lines represent 95% CIs of the cosine. Whiskers indicate 95% CIs of 5-HIAA concentrations.</p

Median CSF 5-HAA Concentrations (in nmol/L) are plotted against Month of CSF Sampling.

<p>Bold line represents cosine, thin line represents LOESS and dashed lines represent 95% CIs of the cosine. Whiskers indicate 95% CIs of 5-HIAA concentrations.</p