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Chunk #29 — Discussion

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Gene expression imputation across multiple brain regions provides insights into schizophrenia risk.
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Finally, we assessed patterns of expression for the 67 SCZ-associated genes throughout development using spatio-temporal transcriptomic data obtained from BRAINSPAN. We identified four clusters of genes, with expression in four distinct spatiotemporal regions, ranging from early pre-natal to strictly post-natal expression. There are plausible hypotheses and genetic evidence for SCZ disease development in adolescence, given the correlation with age of onset, as well as prenatally, supported by genetic overlap with neurodevelopmental disorders69-71 as well as the earlier onset of cognitive impairments72-75. Understanding the temporal expression patterns of SCZ-associated genes can help to elucidate gene development and trajectory, and inform research and analysis design. Identification of SCZ-associated genes primarily expressed prenatally is notable given our adult eQTL reference panels, and may reflect common eQTL architecture across development, which is known to be partial76-78; therefore, our results should spur interest in extending transcriptomic imputation data and/or methods to early development76. Identification of SCZ-associated genes primarily expressed in adolescence and adulthood is of particular interest for direct analysis of the brain transcriptome in adult psychiatric cases.