Transcriptome sequencing study implicates immune-related genes differentially expressed in schizophrenia: New data and a meta-analysis

We undertook an RNA sequencing (RNAseq)-based transcriptomic profiling study on lymphoblastoid cell lines of a European ancestry sample of 529 schizophrenia cases and 660 controls, and found 1058 genes to be differentially expressed by affection status. These differentially expressed genes were enriched for involvement in immunity, especially the 697 genes with higher expression in cases. Comparing the current RNAseq transcriptomic profiling to our previous findings in an array-based study of 268 schizophrenia cases and 446 controls showed a highly significant positive correlation over all genes. Fifteen (18%) of the 84 genes with significant (false discovery rate <.05) expression differences between cases and controls in the previous study and analyzed here again were differentially expressed by affection status here at a genome-wide significance level (Bonferroni Po<.05 adjusted for 8141 analyzed genes in total, or P< ∼ 6.1 × 10^-6), all with the same direction of effect, thus providing corroborative evidence despite each sample of fully independent subjects being studied by different technological approaches. Meta-analysis of the RNAseq and array data sets (797 cases and 1106 controls) showed 169 additional genes (besides those found in the primary RNAseq-based analysis) to be differentially expressed, and provided further evidence of immune gene enrichment. In addition to strengthening our previous array-based gene expression differences in schizophrenia cases versus controls and providing transcriptomic support for some genes implicated by other approaches for schizophrenia, our study detected new genes differentially expressed in schizophrenia. We highlight RNAseq-based differential expression of various genes involved in neurodevelopment and/or neuronal function, and discuss caveats of the approach.