File S1 - Expression of DISC1-Interactome Members Correlates with Cognitive Phenotypes Related to Schizophrenia

Table S1, Details of TaqMan probes used for qRT-PCR. List of TaqMan (Applied Biosystems) probes used to explore expression levels in ten genes of the DISC1 interactome. Probes were chosen to span an intron-exon boundary and to amplify the maximum possible number of isoforms possible. Table S2, Factor loadings of cognitive tasks. Factors with eigenvalues of at least 1 were identified by principal components analysis followed by varimax rotation. For each cognitive test, the function explored is detailed together with the loading of the test on each of the four identified factors. Table S3, Assessment of the effect of gene expression levels on prefrontal cortical activity elicited by the N-back task. Correlations were assessed between gene expression and activity in prefrontal cortex during the N-back task (2-back condition). For each correlation, the Brodmann’s area (BA) involved, Talairach coordinates, k values, z-score, and familywise error (FWE) rate corrected p-value are indicated. Where a p-value did not survive multiple testing correction, this is indicated and the uncorrected p-value is presented. Figure S1, Patterns of co-expression amongst DISC1 pathway genes. Graphical representation of the co-expression patterns amongst DISC1 and nine DISC1-interactor genes. Lines between pairs of genes represent significant positive (continuous lines) and negative (dashed lines) Pearson correlations. Line width represents a visual proxy of correlation strength, as indicated. Figure S2, Heat map representations of the relationship between the expression of DISC1 pathway genes and cognitive performance. Depicted are heat maps representing the relationship between A. changes in PC3 (Phonological Fluency-Speed of Processing) in relation to changes in expression levels of DISC1 and NDEL1, and B. changes in PC4 (Semantic Fluency) in relation to changes in expression levels of DISC1 and AKAP9. Figure S3, Relationship between DISC1 and NDEL1 expression levels and frontal cortex function. The relationship between frontal cortical activity elicited by the N-back task and the expression levels of NDEL1, DISC1, and the interaction between NDEL1 and DISC1 expression was assessed using the general linear model. A. Heat map graphical representation of changes in fMRI BOLD signal in BA 6 during the N-back task in relation to changes in expression levels of DISC1 and NDEL1. B. Negative main effect of NDEL1 expression level on BA 6 activity during the N-back task when including NDEL1 expression level, DISC1 expression level and the DISC1-by-NDEL1 interaction term in the model. C. Negative main effect of DISC1 expression level on BA 6 activity during the N-back task when including NDEL1 expression level, DISC1 expression level and the NDEL1-by-DISC1 interaction term in the model. D. Positive effect of the interaction term, DISC1-by-NDEL1 expression level, on BA 6 activity during the N-back task when including NDEL1, DISC1, and the DISC1-by-NDEL1 interaction term in the model. Figure S4, Relationship between AKAP9 and DISC1 expression levels and prefrontal cortex function. The relationship between frontal cortical activity elicited by the N-back task and the expression levels of AKAP9, DISC1, and the interaction between AKAP9 and DISC1 expression was assessed using the general linear model. The model included AKAP9 expression level, DISC1 expression level and the AKAP9-by-DISC1 interaction. A. Heat map graphical representation of changes in fMRI BOLD signal in BA 6 during the N-back task in relation to changes in expression levels of DISC1 and AKAP9. B. Positive main effect of DISC1 expression level on BA 9 activity during the N-back task when including AKAP9 expression level, DISC1 expression level and the DISC1-by-AKAP9 interaction term in the model. C. Positive main effect of AKAP9 expression level on BA 9 activity during the N-back task when including AKAP9 expression level, DISC1 expression level and the DISC1-by-AKAP9 interaction term in the model. D. Negative effect of the AKAP9-by-DISC1 interaction on BA 9 activity during the N-back task when including AKAP9, DISC1 and the DISC1-by-AKAP9 interaction term in the model. (DOC)