Effect of functional variants on gene expression in human brain

V Strumba; T Blackwell; E Sliwerska; J Li; AJ Schatzberg; EG Jones; WE Bunney; RM Myers; H Akil SJ Watson; M Burmeister R Bernard
European Conference on Computational Biology. 2007.


Since the completion of the Human Genome Project, major efforts such as HapMap project now concentrate on identifying and cataloging human polymorphisms such as SNPs and deletions. Even if an association between a phenotype and a SNP is found, the mechanism of how these variations change the phenotype remains a mystery. Here, we address this question by searching for a downstream molecular phenotype of common genetic variants that have been shown to be functional (either affecting mRNA levels or protein function). We chose a number of polymorphisms that have been previously found associated with behavior or psychiatric disorders, and tested for association of these genetic variants with expression levels of thousands of genes in human postmortem brain samples, as measured on Affymetrix expression microarrays. Brain samples were from subjects that died relatively suddenly (i.e. did not spend extended time in "agonal" state in the hospital), and were either controls without any psychiatric illness, or had a diagnosis of depression, bipolar disorder or schizophrenia. mRNA was isolated from eight brain regions that were dissected either anatomically or by laser capture microscoscopy.