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

TitleWhole-Genome and RNA Sequencing Reveal Variation and Transcriptomic Coordination in the Developing Human Prefrontal Cortex.
Publication TypeJournal Article
Year of Publication2020
AuthorsWerling, DM, Pochareddy, S, Choi, J, An, J-Y, Sheppard, B, Peng, M, Li, Z, Dastmalchi, C, Santpere, G, Sousa, AMM, Tebbenkamp, ATN, Kaur, N, Gulden, FO, Breen, MS, Liang, L, Gilson, MC, Zhao, X, Dong, S, Klei, L, A Cicek, E, Buxbaum, JD, Adle-Biassette, H, Thomas, J-L, Aldinger, KA, O'Day, DR, Glass, IA, Zaitlen, NA, Talkowski, ME, Roeder, K, State, MW, Devlin, B, Sanders, SJ, Sestan, N
JournalCell Rep
Volume31
Issue1
Pagination107489
Date Published2020 Apr 07
ISSN2211-1247
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.

DOI10.1016/j.celrep.2020.03.053
Alternate JournalCell Rep
PubMed ID32268104
Grant ListR01 MH110928 / MH / NIMH NIH HHS / United States
R01 CA227237 / CA / NCI NIH HHS / United States
R03 DE025665 / DE / NIDCR NIH HHS / United States
R01 MH109901 / MH / NIMH NIH HHS / United States
U01 HG009080 / HG / NHGRI NIH HHS / United States
U01 MH111662 / MH / NIMH NIH HHS / United States