On the outside, looking in: A review and evaluation of the comparability of blood and brain “‐omes”

In this article, we review studies detailing the correspondence between peripheral blood and brain tissue across various domains of high-throughput -omic analysis in order to provide a context for evaluating blood-based biomarker studies. Specifically, we reviewed seven studies comparing patterns of DNA methylation (i.e., an aspect of the epigenome), eight articles comparing patterns of gene expression (i.e., the transcriptome), and three articles comparing patterns of protein expression (i.e., the proteome). Our review of the epigenomic literature suggests that CpG-island methylation levels are generally highly correlated (r = 0.90) between blood and brain. Our review of transcriptomic studies suggests that between 35% and 80% of known transcripts are present in both brain and blood tissue samples; estimates of cross-tissue correlation in expression levels were found to range from 0.25 to 0.64, with stronger correlations observed among particular subsets of genes. Relative to the epigenome and transcriptome, the proteome has not been as fully compared between brain and blood samples, highlighting an important area for future work as whole-proteome profiling methods mature. Beyond reviewing the relevant studies, we discuss some of the assumptions, methodological issues, and gaps in knowledge that should be addressed in order to better understand how the multiple "-omes" of the brain are reflected in the peripheral blood. A better understanding of these relationships is a critical precursor to the validation of biomarkers for brain disorders.