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DOI | 10.1126/science.aat8127 |
Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder | |
Gandal, Michael J.1,2,3,4; Zhang, Pan5; Hadjimichael, Evi6,7,8,9,10,11; Walker, Rebecca L.2,3,4; Chen, Chao12,13; Liu, Shuang14,15,16; Won, Hyejung2,3,4,17,18; van Bakel, Harm8,9; Varghese, Merina11,19; Wang, Yongjun20; Shieh, Annie W.21; Haney, Jillian1,2,3; Parhami, Sepideh1,2,3; Belmont, Judson6,7,8,9,10,11; Kim, Minsoo1,4; Losada, Patricia Moran5; Khan, Zenab8,9; Mleczko, Justyna22,23; Xia, Yan12,21; Dai, Rujia12,21; Wang, Daifeng24; Yang, Yucheng T.14,15,16; Xu, Min14,15,16; Fish, Kenneth22,23; Hof, Patrick R.7,11,19; Warrell, Jonathan14,15,16; Fitzgerald, Dominic25; White, Kevin25,26,27; Jaffe, Andrew E.28,29,30; Peters, Mette A.31; Gerstein, Mark14,15,16; Liu, Chunyu12,21,32; Iakoucheva, Lilia M.5; Pinto, Dalila6,7,8,9,10,11; Geschwind, Daniel H.1,2,3,4 | |
2018-12-14 | |
发表期刊 | SCIENCE
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ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2018 |
卷号 | 362期号:6420页码:1265-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Peoples R China |
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 likely mediated 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. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000452994400042 |
WOS关键词 | LONG NONCODING RNAS ; GENETIC-VARIATION ; EXPRESSION PATTERNS ; IMMUNE-RESPONSE ; POLYGENIC RISK ; CELL-TYPES ; AUTISM ; GENOME ; BRAIN ; ASSOCIATION |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/200318 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst, Dept Psychiat, 695 Charles E Young Dr South, Los Angeles, CA 90095 USA; 2.Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst, Program Neurobehav Genet, Los Angeles, CA 90095 USA; 3.Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst, Dept Neurol,Ctr Autism Res & Treatment, 695 Charles E Young Dr South, Los Angeles, CA 90095 USA; 4.Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA; 5.Univ Calif San Diego, Dept Psychiat, 9500 Gilman Dr, La Jolla, CA 92093 USA; 6.Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA; 7.Icahn Sch Med Mt Sinai, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA; 8.Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA; 9.Icahn Sch Med Mt Sinai, Icahn Inst Data Sci & Genom Technol, New York, NY 10029 USA; 10.Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA; 11.Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA; 12.Cent S Univ, Sch Life Sci, Changsha 410078, Hunan, Peoples R China; 13.Cent S Univ, Natl Clin Res Ctr Geriatr Disorders, Changsha 410078, Hunan, Peoples R China; 14.Yale Univ, Dept Mol Biophys & Biochem, Program Computat Biol & Bioinformat, New Haven, CT 06520 USA; 15.Yale Univ, Dept Comp Sci, Program Computat Biol & Bioinformat, New Haven, CT 06520 USA; 16.Yale Univ, Dept Stat & Data Sci, Program Computat Biol & Bioinformat, New Haven, CT 06520 USA; 17.Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA; 18.Univ N Carolina, UNC Neurosci Ctr, Chapel Hill, NC 27599 USA; 19.Icahn Sch Med Mt Sinai, Fishberg Dept Neurosci, New York, NY 10029 USA; 20.Cent S Univ, Xiangya Hosp 1, Changsha 410011, Hunan, Peoples R China; 21.SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA; 22.Icahn Sch Med Mt Sinai, Cardiovasc Res Ctr, Dept Med, New York, NY 10029 USA; 23.Icahn Sch Med Mt Sinai, Cardiovasc Res Ctr, Dept Cardiol, New York, NY 10029 USA; 24.SUNY Stony Brook, Dept Biomed Informat, Stony Brook, NY 11794 USA; 25.Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA; 26.Univ Chicago, Inst Genom & Syst Biol, Chicago, IL 60637 USA; 27.Tempus Labs, Chicago, IL 60654 USA; 28.Lieber Inst Brain Dev, Baltimore, MD 21205 USA; 29.Johns Hopkins Sch Med, Dept Psychiat, Baltimore, MD 21287 USA; 30.Johns Hopkins Sch Med, Dept Behav Sci, Baltimore, MD 21287 USA; 31.Sage Bionetworks, CNS Data Coordinat Grp, Seattle, WA 98109 USA; 32.Shaanxi Normal Univ, Sch Psychol, Xian 710000, Shaanxi, Peoples R China |
推荐引用方式 GB/T 7714 | Gandal, Michael J.,Zhang, Pan,Hadjimichael, Evi,et al. Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder[J]. SCIENCE,2018,362(6420):1265-+. |
APA | Gandal, Michael J..,Zhang, Pan.,Hadjimichael, Evi.,Walker, Rebecca L..,Chen, Chao.,...&Geschwind, Daniel H..(2018).Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder.SCIENCE,362(6420),1265-+. |
MLA | Gandal, Michael J.,et al."Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder".SCIENCE 362.6420(2018):1265-+. |
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