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Whole-Genome and RNA Sequencing Reveal Variation and Transcriptomic Coordination in the Developing Human Prefrontal Cortex

Authors
Werling, Donna M.Pochareddy, SirishaChoi, JinmyungAn, Joon-YongSheppard, BrookePeng, MinshiLi, ZhenDastmalchi, ClaudiaSantpere, GabrielSousa, Andre M. M.Tebbenkamp, Andrew T. N.Kaur, NavjotGulden, Forrest O.Breen, Michael S.Liang, LindsayGilson, Michael C.Zhao, XuefangDong, ShanKlei, LambertusCicek, A. ErcumentBuxbaum, Joseph D.Adle-Biassette, HomaThomas, Jean-LeonAldinger, Kimberly A.O'Day, Diana R.Glass, Ian A.Zaitlen, Noah A.Talkowski, Michael E.Roeder, KathrynState, Matthew W.Devlin, BernieSanders, Stephan J.Sestan, Nenad
Issue Date
7-4월-2020
Publisher
CELL PRESS
Keywords
BrainVar; DLPFC; dorsolateral prefrontal cortex; fetal transition; LOC101926933 RP11-298I3.1 AL132780.1 ENSG00000257285; mTOR; prenatal eQTL; PsychENCODE; RHEBL1
Citation
CELL REPORTS, v.31, no.1
Indexed
SCIE
SCOPUS
Journal Title
CELL REPORTS
Volume
31
Number
1
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/56642
DOI
10.1016/j.celrep.2020.03.053
ISSN
2211-1247
Abstract
Gene expression levels vary across developmental stage, cell type, and region in the brain. Genomic variants also contribute to the variation in expression, and some neuropsychiatric disorder loci may exert their effects through this mechanism. To investigate these relationships, we present BrainVar, a unique resource of paired whole-genome and bulk tissue RNA sequencing from the dorsolateral prefrontal cortex of 176 individuals across prenatal and postnatal development. Here we identify common variants that alter gene expression (expression quantitative trait loci [eQTLs]) constantly across development or predominantly during prenatal or postnatal stages. Both "constant" and "temporal-predominant" eQTLs are enriched for loci associated with neuropsychiatric traits and disorders and colocalize with specific variants. Expression levels of more than 12,000 genes rise or fall in a concerted late-fetal transition, with the transitional genes enriched for cell-type-specific genes and neuropsychiatric risk loci, underscoring the importance of cataloging developmental trajectories in understanding cortical physiology and pathology.
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