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

Autor:	Werling DM; Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA; Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI 53706, USA., Pochareddy S; Department of Neuroscience and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA., Choi J; Department of Neuroscience and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA., An JY; Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Integrated Biomedical and Life Science, Korea University, Seoul 02841, Republic of Korea; School of Biosystem and Biomedical Science, College of Health Science, Korea University, Seoul 02841, Republic of Korea., Sheppard B; Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA., Peng M; Department of Statistics and Data Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA., Li Z; Department of Neuroscience and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA; Department of Neurosciences, University of California, San Diego, San Diego, CA 92093, USA., Dastmalchi C; Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA., Santpere G; Department of Neuroscience and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA; Neurogenomics Group, Research Programme on Biomedical Informatics, Hospital del Mar Medical Research Institute, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Catalonia, Spain., Sousa AMM; Department of Neuroscience and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA., Tebbenkamp ATN; Department of Neuroscience and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA., Kaur N; Department of Neuroscience and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA., Gulden FO; Department of Neuroscience and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA., Breen MS; Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Liang L; Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA., Gilson MC; Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA., Zhao X; Center for Genomic Medicine and Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Neurology, Harvard Medical School, Boston, MA 02115, USA; Program in Medical and Population Genetics and Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA 02142, USA., Dong S; Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA., Klei L; Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA., Cicek AE; Department of Computer Engineering, Bilkent University, Ankara 06800, Turkey; Computational Biology Department, Carnegie Mellon University, Pittsburgh, PA 15213, USA., Buxbaum JD; Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Adle-Biassette H; Department of Pathology, Lariboisière Hospital, APHP, Biobank BB-0033-00064, and Université de Paris, 75006 Paris, France., Thomas JL; Department of Neurology, Yale University School of Medicine, New Haven, CT 06511, USA; UMRS1127, Sorbonne Université, Institut du Cerveau et de la Moelle Épinière, 75013 Paris, France., Aldinger KA; Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA 98101, USA; Brotman Baty Institute for Precision Medicine, Seattle, WA 98195, USA., O'Day DR; Department of Pediatrics, University of Washington, Seattle, WA 98105, USA., Glass IA; Department of Pediatrics, University of Washington, Seattle, WA 98105, USA., Zaitlen NA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA., Talkowski ME; Center for Genomic Medicine and Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Neurology, Harvard Medical School, Boston, MA 02115, USA; Program in Medical and Population Genetics and Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA 02142, USA., Roeder K; Department of Statistics and Data Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA; Computational Biology Department, Carnegie Mellon University, Pittsburgh, PA 15213, USA., State MW; Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA 94158, USA., Devlin B; Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA., Sanders SJ; Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: stephan.sanders@ucsf.edu., Sestan N; Department of Neuroscience and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Comparative Medicine, Program in Integrative Cell Signaling and Neurobiology of Metabolism, Yale School of Medicine, New Haven, CT 06510, USA; Program in Cellular Neuroscience, Neurodegeneration, and Repair and Yale Child Study Center, Yale School of Medicine, New Haven, CT 06510, USA. Electronic address: nenad.sestan@yale.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2020 Apr 07; Vol. 31 (1), pp. 107489.
DOI:	10.1016/j.celrep.2020.03.053
Abstrakt:	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. Competing Interests: Declaration of Interests The authors declare no competing interests. (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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