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Chunk #18 — Association Studies — Quantitation of relative allelic expression

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Fine mapping of ZNF804A and genome-wide significant evidence for its involvement in schizophrenia and bipolar disorder.
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To isolate cis-effects from trans-effects on gene expression in human brain, we measured the relative expression of each parental copy of ZNF804A in post mortem brain mRNA taken from individuals heterozygous for expressed SNP rs4667001, a marker that is in strong LD (D’=1) with rs1344706 in that brain series (D’=0.95 in our association sample). We have described the methodology and the samples (derived from cerebral cortex of 149 unrelated anonymous individuals (86M, 63F; mean age = 58, SD = 19)) in detail elsewhere(19). Since this method uses the level of mRNA expressed from one parental chromosome to control for that expressed by the other, the assay is controlled for (and therefore requires no adjustment for) common confounders that affect more standard measurements of mRNA in native human tissue (e.g. drug exposure, agonal state, post-mortem delay, pH, age etc).