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DOI | 10.1126/science.aat8127 |
Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder | |
Gandal M.J.; Zhang P.; Hadjimichael E.; Walker R.L.; Chen C.; Liu S.; Won H.; Van Bakel H.; Varghese M.; Wang Y.; Shieh A.W.; Haney J.; Parhami S.; Belmont J.; Kim M.; Losada P.M.; Khan Z.; Mleczko J.; Xia Y.; Dai R.; Wang D.; Yang Y.T.; Xu M.; Fish K.; Hof P.R.; Warrell J.; Fitzgerald D.; White K.; Jaffe A.E.; Peters M.A.; Gerstein M.; Liu C.; Iakoucheva L.M.; Pinto D.; Geschwind D.H. | |
发表日期 | 2018 |
ISSN | 0036-8075 |
卷号 | 362期号:6420 |
英文摘要 | Most genetic risk for psychiatric disease lies in regulatory regions, implicating pathogenic dysregulation of gene expression and splicing. However, comprehensive assessments of transcriptomic organization in diseased brains are limited. In this work, we integrated genotypes and RNA sequencing in brain samples from 1695 individuals with autism spectrum disorder (ASD), schizophrenia, and bipolar disorder, as well as controls. More than 25% of the transcriptome exhibits differential splicing or expression, with isoform-level changes capturing the largest disease effects and genetic enrichments. Coexpression networks isolate disease-specific neuronal alterations, as well as microglial, astrocyte, and interferon-response modules defining previously unidentified neural-immune mechanisms.We integrated genetic and genomic data to perform a transcriptome-wide association study, prioritizing disease loci likelymediated by cis effects on brain expression.This transcriptome-wide characterization of the molecular pathology across three major psychiatric disorders provides a comprehensive resource for mechanistic insight and therapeutic development. © 2018 American Association for the Advancement of Science. All rights reserved. |
英文关键词 | RNA isoform; transcriptome; untranslated RNA; isoprotein; transcriptome; assessment method; autism; brain; disability; gene expression; genetic analysis; genotype; immune response; pathology; risk factor; Article; astrocyte; autism; bipolar disorder; brain dysfunction; cohort analysis; controlled study; disease classification; gene expression; gene mutation; gene switching; genetic association; genetic risk; genetic variability; genome-wide association study; human; illness trajectory; interneuron; Mendelian randomization analysis; microglia; molecular pathology; neuropathology; phenotype; priority journal; RNA sequence; RNA splicing; schizophrenia; transcriptomics; autism; bipolar disorder; brain; genetic predisposition; genetics; metabolism; RNA splicing; schizophrenia; sequence analysis; Autism Spectrum Disorder; Bipolar Disorder; Brain; Genetic Predisposition to Disease; Humans; Protein Isoforms; RNA Splicing; Schizophrenia; Sequence Analysis, RNA; Transcriptome |
语种 | 英语 |
来源期刊 | Science |
文献类型 | 期刊论文 |
条目标识符 | http://gcip.llas.ac.cn/handle/2XKMVOVA/243774 |
作者单位 | Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, 695 Charles E. Young Drive South, Los Angeles, CA 90095, United States; Program in Neurobehavioral Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, United States; Department of Neurology, Center for Autism Research and Treatment, University of California, Los Angeles, 695 Charles E. Young Drive South, Los Angeles, CA 90095, United States; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, United States; Department of Psychiatry, University of California San Diego, 9500 Gilman Dr., San Diego, CA 92093, United States; Department of Psychiatry, Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States; Department of Genetics and Genomic Sciences, Icahn Institute for Data Science and Genomic Technology, Icahn School of Medi... |
推荐引用方式 GB/T 7714 | Gandal M.J.,Zhang P.,Hadjimichael E.,et al. Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder[J],2018,362(6420). |
APA | Gandal M.J..,Zhang P..,Hadjimichael E..,Walker R.L..,Chen C..,...&Geschwind D.H..(2018).Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder.Science,362(6420). |
MLA | Gandal M.J.,et al."Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder".Science 362.6420(2018). |
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