Analysis of whole genome biomarker expression in blood and brain

Abstract

The consistency of peripheral gene expression data and the overlap with brain expression has not been evaluated in biomarker discovery, nor has it been reported in multiple tissues from the same subjects on a genome wide transcript level. The effects of processing whole blood, transformation, and passaged cell lines on gene expression profiling was studied in healthy subjects using Affymetrix arrays. Ficoll extracted peripheral blood mononuclear cells (PBMCs), Epstein-Barr virus (EBV) transformed lymphocytes, passaged lymphoblastic cell lines (LCLs), and whole blood from Tempus tubes were compared. There were 6,813 transcripts differentially expressed between different methods of blood preparation. Principal component analysis resolved two partitions involving pre- and post-transformation EBV effects. Combining results from Affymetrix arrays, postmortem subjects' brain and PBMC profiles showed co-expression levels of summarized transcripts for 4,103 of 17,859 (22.9%) RefSeq transcripts. In a control experiment, rat hemi-brain and blood showed similar expression levels for 19% of RefSeq transcripts. After filtering transcripts that were not significantly different in abundance between human cerebellum and PBMCs from the Affymetrix exon array the correlation in mean transcript abundance was high as expected (r = 0.98). Differences in the alternative splicing index in brain and blood were found for about 90% of all transcripts examined. This study demonstrates over 4,100 brain transcripts co-expressed in blood samples can be further examined by in vitro and in vivo experimental studies of blood and cell lines from patients with psychiatric disorders.

Dexamethasone Stimulated Gene Expression in Peripheral Blood is a Sensitive Marker for Glucocorticoid Receptor Resistance in Depressed Patients

“…Although gene expression profiles in peripheral blood cells are not likely to reflect profiles in neuronal cell populations, there is an overlap between gene activity measures in brain and peripheral blood. Sullivan et al (2006) found a median correlation of 0.5 between transcripts expressed in both whole blood and the central nervous system and a study by (Rollins et al (2010) showed that over 4000 transcripts are co-expressed in blood cells and postmortem brain tissue. Additionally, glucocorticoids have effects on peripheral blood cells and the hypothalamus-pituitary adrenal (HPA) axis, which is perturbed during depressive episodes of many patients (Gladkevich et al, 2004).…”

Peripheral Endocannabinoid System Dysregulation in First-Episode Psychosis

“…The identification of accessible blood biological markers for psychotic disorders is one of the main needs for both patients and psychiatrists for early diagnosis and evolution monitoring (Schwarz et al, 2012), maybe being the best option to approach to their cerebral expression (Rollins et al, 2010). Taking into account the results of our multivariable analysis, a low expression of DAGL and NAPE or a high expression of FAAH and NAPE would be associated to a highest risk of suffering a FEP.…”

Biomarkers in schizophrenia: A focus on blood based diagnostics and theranostics

“…In addition, the strong heritability of Sz suggests that there may be genetic markers detectable in peripheral tissue [12] . Finally, there are data that suggest changes in gene expression [13,14] , epigenetic patterns [15] , proteo mic/metabolic markers [1618] and functional cellular pathways [16,1921] are present in both the peripheral and central nervous system (CNS) tissue. More recently our concepts about the interactions between the brain and periphery have been expanded with data suggesting that the CNS may influence gene expression and metabolism in the peripheral blood via cytokines, neurotransmitters, or hormones [22,23] , while immunerelated alterations in the CNS may in turn originate from peripheral blood [10,24] ( Figure 1).…”