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Gandal, Michael J; Zhang, Pan; Hadjimichael, Evi; Walker, Rebecca L; Chen, Chao; Liu, Shuang; Won, Hyejung; van Bakel, Harm; Varghese, Merina; Wang, Yongjun; Shieh, Annie W; Haney, Jillian; Parhami, Sepideh; Belmont, Judson; Kim, Minsoo; Moran Losada, Patricia; Khan, Zenab; Mleczko, Justyna; Xia, Yan; Dai, Rujia; Wang, Daifeng; Yang, Yucheng T; Xu, Min; Fish, Kenneth; Hof, Patrick R; Warrell, Jonathan; Fitzgerald, Dominic; White, Kevin; Jaffe, Andrew E; Peters, Mette A; Gerstein, Mark; Liu, Chunyu; Iakoucheva, Lilia M; Pinto, Dalila; Geschwind, Daniel H
Science, 12/2018, Letnik: 362, Številka: 6420Journal Article
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.
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Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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