Pulse Brain · Growing Health Evidence Index
Peer-reviewed

Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder

Michael J. Gandal, Pan Zhang, Evi Hadjimichael, Rebecca L. Walker, Chao Chen, Shuang Liu, Hyejung Won, Harm van Bakel, Merina Varghese, Yongjun Wang, Annie W. Shieh, Jillian R. Haney, Sepideh Parhami, Judson Belmont, Minsoo Kim, Patricia Morán Losada, Zenab Khan, Justyna Mleczko, Yan Xia, Rujia Dai, Daifeng Wang, Yucheng Yang, Min Xu, Kenneth Fish, Patrick R. Hof, Jonathan Warrell, Dominic Fitzgerald, Kevin P. White, Andrew E. Jaffe, Mette A. Peters, Mark Gerstein, Chunyu Liu, Lilia M. Iakoucheva, Dalila Pinto, Daniel H. Geschwind, Allison E. Ashley‐Koch, Gregory E. Crawford, Melanie E. Garrett, Lingyun Song, Alexias Safi, Graham D. Johnson, Gregory A. Wray, Timothy E. Reddy, Fernando S. Goes, Peter P. Zandi, Julien Bryois, Andrew E. Jaffe, Amanda J. Price, Nikolay A. Ivanov, Leonardo Collado‐Torres, Thomas M. Hyde, Emily E. Burke, Joel E. Kleiman, Ran Tao, Joo Heon Shin, Schahram Akbarian, Kiran Girdhar, Yan Jiang, Marija Kundaković, Leanne Brown, Bibi Kassim, Royce Park, Jennifer Wiseman, Elizabeth Zharovsky, Rivka Jacobov, Olivia Devillers, Elie Flatow, Gabriel E. Hoffman, Barbara K. Lipska, David A. Lewis, Vahram Haroutunian, Chang-Gyu Hahn, Alexander W. Charney, Stella Dracheva, Alexey Kozlenkov, Judson Belmont, Diane M. Del Valle, Nancy Francoeur, Evi Hadjimichael, Dalila Pinto, Harm van Bakel, Panos Roussos, John F. Fullard, Jaroslav Bendl, Mads E. Hauberg, Lara M. Mangravite, Mette A. Peters, Yooree Chae, Junmin Peng, Mingming Niu, Xusheng Wang, Maree J. Webster, Thomas G. Beach, Chao Chen, Yi Jiang, Rujia Dai, Annie W. Shieh, Chunyu Liu, Kay Grennan, Yan Xia

Science · 2018

Read source ↗ All evidence

Summary

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 int

Source type
Peer-reviewed study
DOI
10.1126/science.aat8127
Catalogue ID
SNmoj7nvsf-6d4aa6
Pulse AI · ask about this record

Dig deeper with Pulse AI.

Pulse AI has read the whole catalogue. Ask about this record, its theme, or how the findings apply to UK farming and policy — every answer cites the underlying studies.