@article{44669127b5b14b02b2009b36346242a7,
title = "Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders",
abstract = "Cellular heterogeneity in the human brain obscures the identification of robust cellular regulatory networks, which is necessary to understand the function of non-coding elements and the impact of non-coding genetic variation. Here we integrate genome-wide chromosome conformation data from purified neurons and glia with transcriptomic and enhancer profiles, to characterize the gene regulatory landscape of two major cell classes in the human brain. We then leverage cell-type-specific regulatory landscapes to gain insight into the cellular etiology of several brain disorders. We find that Alzheimer{\textquoteright}s disease (AD)-associated epigenetic dysregulation is linked to neurons and oligodendrocytes, whereas genetic risk factors for AD highlighted microglia, suggesting that different cell types may contribute to disease risk, via different mechanisms. Moreover, integration of glutamatergic and GABAergic regulatory maps with genetic risk factors for schizophrenia (SCZ) and bipolar disorder (BD) identifies shared (parvalbumin-expressing interneurons) and distinct cellular etiologies (upper layer neurons for BD, and deeper layer projection neurons for SCZ). Collectively, these findings shed new light on cell-type-specific gene regulatory networks in brain disorders.",
author = "{The PsychENCODE Consortium} and Benxia Hu and Hyejung Won and Won Mah and Park, {Royce B.} and Bibi Kassim and Keeley Spiess and Alexey Kozlenkov and Crowley, {Cheynna A.} and Sirisha Pochareddy and Ashley-Koch, {Allison E.} and Crawford, {Gregory E.} and Garrett, {Melanie E.} and Lingyun Song and Alexias Safi and Johnson, {Graham D.} and Wray, {Gregory A.} and Reddy, {Timothy E.} and Goes, {Fernando S.} and Peter Zandi and Julien Bryois and Jaffe, {Andrew E.} and Price, {Amanda J.} and Ivanov, {Nikolay A.} and Leonardo Collado-Torres and Hyde, {Thomas M.} and Burke, {Emily E.} and Kleiman, {Joel E.} and Ran Tao and Shin, {Joo Heon} and Kiran Girdhar and Yan Jiang and Marija Kundakovic and Leanne Brown and Wiseman, {Jennifer R.} and Elizabeth Zharovsky and Rivka Jacobov and Olivia Devillers and Elie Flatow and Hoffman, {Gabriel E.} and Judson Belmont and {Del Valle}, Diane and Nancy Francoeur and Evi Hadjimichael and Dalila Pinto and {van Bakel}, Harm and Panos Roussos and Fullard, {John F.} and Jaroslav Bendl and Hauberg, {Mads E.} and Miller, {Daniel J.}",
note = "Funding Information: We thank members of the Won lab for helpful discussions and comments about this paper. We also thank Sergio Espeso Gil for transferring RNA-seq datasets from NeuN+ and NeuN− cells. This research was supported by the National Institute of Health (NIMH: P50MH106438, R01MH094714, U01MH103339, R01MH110927, R01MH100027, D.H.G.; R00MH113823, DP2MH122403, R21DA051921, R01AG066871, H.W.; U01MH103392, S.A.; R21MH103877, U01MH122590, R01DA044940, S.D.), the Veterans Administration Biomedical Laboratory Research & Development (I01BX002876, S.D.), a NARSAD Young Investigator Award from the Brain and Behavior Research Foundation (H.W.), a SPARK grant from the Simons Foundation Autism Research Initiative (H.W.), and Helen Lyng White Fellowship (W.M.). We also acknowledge the support from the Data Science Core at the UNC IDDRC (P50HD103573). The DLPFC tissue used in this research was obtained from the Human Brain Collection Core, Intramural Research Program, NIMH (http://www.nimh.nih.gov/ hbcc). We thank Drs. Stefano Marenco, Barbara Lipska, and Pavan Auluck for their assistance in tissue procurement. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = dec,
doi = "10.1038/s41467-021-24243-0",
language = "English (US)",
volume = "12",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}