A cross-laboratory comparison of expression profiling data from normal human postmortem brain.
Expression profiling of post-mortem human brain tissue has been widely used to study molecular changes associated with neuropsychiatric diseases as well as normal processes such as aging. Changes in expression associated with factors such as age, gender or postmortem interval are often more pronounced than changes associated with disease. Therefore in addition to being of interest in their own right, careful consideration of these effects are important in the interpretation of disease studies. We performed a large meta-analysis of genome-wide expression studies of normal human cortex to more fully catalogue the effects of age, gender, postmortem interval and brain pH, yielding a "meta-signature" of gene expression changes for each factor. We validated our results by showing a significant overlap with independent gene lists extracted from the literature. Importantly, meta-analysis identifies genes which are not significant in any individual study. Finally, we show that many schizophrenia candidate genes appear in the meta-signatures, reinforcing the idea that studies must be carefully controlled for interactions between these factors and disease. In addition to the inherent value of the meta-signatures, our results provide critical information for future studies of disease effects in the human brain.
Mistry
M
M
Canadian Institute of Health Research/Michael Smith Foundation for Health Research (CIHR/MSFHR) Graduate Program in Bioinformatics, University of British Columbia, BC, Canada.
Pavlidis
P
P
D000367:Age Factors; D001921:Brain / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D011180:Postmortem Changes