Assessing the validity of blood‐based gene expression profiles for the classification of schizophrenia and bipolar disorder: A preliminary report

Abstract

Recent advances have facilitated the use of blood-derived RNA to conduct genomic analyses of human diseases. This emerging technology represents a rigorous and convenient alternative to traditional tissue biopsy-derived RNA, as it allows for larger sample sizes, better standardization of technical procedures, and the ability to non-invasively profile human subjects. In the present pilot study, we have collected RNA from blood of patients diagnosed with schizophrenia or bipolar disorder (BPD), as well as normal control subjects. Using microarray analysis, we found that each disease state exhibited a unique expressed genome signature, allowing us to discriminate between the schizophrenia, BPD, and control groups. In addition, we validated changes in several potential biomarker genes for schizophrenia and BPD by RT-PCR, and some of these were found to code to chromosomal loci previously linked to schizophrenia. Linear and non-linear combinations of eight putative biomarker genes (APOBEC3B, ADSS, ATM, CLC, CTBP1, DATF1, CXCL1, and S100A9) were able to discriminate between schizophrenia, BPD, and control samples, with an overall accuracy of 95%-97% as indicated by receiver operating characteristic (ROC) curve analysis. We therefore propose that blood cell-derived RNA may have significant value for performing diagnostic functions and identifying disease biomarkers in schizophrenia and BPD.

Genome-wide expression analysis of peripheral blood identifies candidate biomarkers for schizophrenia

“…Several previous reports found differentially expressed genes in peripheral blood of patients with schizophrenia compared to their unaffected siblings (Vawter et al 2004;Middleton et al 2005;Kakiuchi et al 2008) or to controls Tsuang et al 2005;Numata et al 2007). The usual confounders include methodological differences in data collection, heterogeneity of clinical presentations of the illness (Numata et al 2007) and medications used by study subjects (Colantuoni et al 2008).…”

Are retinoids potential therapeutic agents in disorders of social cognition including autism?

“…One group of biomarkers for neuropsychiatric disorders that shows considerable promise is blood gene expression profiling [108][109][110][111][112][113]. Most of the studies to date have focused on human lymphocytes gene expression profiling, comparison between illness groups and normal controls, and cross-matching with human postmortem brain gene expression data.…”

Expression QTL analysis of top loci from GWAS meta-analysis highlights additional schizophrenia candidate genes

“…[16][17][18][19][20][21][22] Therefore, gene expression profiling in blood may provide additional insight into the etiology of the disease. We performed the gene expression analyses using whole-blood samples of a relatively large sample of schizophrenia patients and controls.…”