Is human blood a good surrogate for brain tissue in transcriptional studies?
BACKGROUND
Since human brain tissue is often unavailable for transcriptional profiling studies, blood expression data is frequently used as a substitute. The underlying hypothesis in such studies is that genes expressed in brain tissue leave a transcriptional footprint in blood. We tested this hypothesis by relating three human brain expression data sets (from cortex, cerebellum and caudate nucleus) to two large human blood expression data sets (comprised of 1463 individuals).


RESULTS
We found mean expression levels were weakly correlated between the brain and blood data (r range: [0.24,0.32]). Further, we tested whether co-expression relationships were preserved between the three brain regions and blood. Only a handful of brain co-expression modules showed strong evidence of preservation and these modules could be combined into a single large blood module. We also identified highly connected intramodular "hub" genes inside preserved modules. These preserved intramodular hub genes had the following properties: first, their expression levels tended to be significantly more heritable than those from non-preserved intramodular hub genes (p < 10⁻⁹⁰); second, they had highly significant positive correlations with the following cluster of differentiation genes: CD58, CD47, CD48, CD53 and CD164; third, a significant number of them were known to be involved in infection mechanisms, post-transcriptional and post-translational modification and other basic processes.


CONCLUSIONS
Overall, we find transcriptome organization is poorly preserved between brain and blood. However, the subset of preserved co-expression relationships characterized here may aid future efforts to identify blood biomarkers for neurological and neuropsychiatric diseases when brain tissue samples are unavailable.
Cai
Chaochao
C
Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
Langfelder
Peter
P
Fuller
Tova F
TF
Oldham
Michael C
MC
Luo
Rui
R
van den Berg
Leonard H
LH
Ophoff
Roel A
RA
Horvath
Steve
S
D015703:Antigens, CD / Q000235:genetics; D001769:Blood / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005796:Genes; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D058977:Molecular Sequence Annotation; D009928:Organ Specificity / Q000235:genetics; D014158:Transcription, Genetic
D015703:Antigens, CD