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., Moran Losada, P., 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., Psych; ENCODE Consortium, Peters, M. A., Gerstein, M., Liu, C., Iakoucheva, L. M., Pinto, D., Geschwind, D. H.
American Association for the Advancement of Science (AAAS)
Published 2018
American Association for the Advancement of Science (AAAS)
Published 2018
| Publication Date: |
2018-12-14
|
|---|---|
| Publisher: |
American Association for the Advancement of Science (AAAS)
|
| Print ISSN: |
0036-8075
|
| Electronic ISSN: |
1095-9203
|
| Topics: |
Biology
Chemistry and Pharmacology
Geosciences
Computer Science
Medicine
Natural Sciences in General
Physics
|
| Keywords: |
Genetics, Online Only
|
| Published by: |
| _version_ | 1836399104730595328 |
|---|---|
| autor | 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., Moran Losada, P., 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., Psych; ENCODE Consortium, Peters, M. A., Gerstein, M., Liu, C., Iakoucheva, L. M., Pinto, D., Geschwind, D. H. |
| beschreibung | 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. |
| citation_standardnr | 6369582 |
| datenlieferant | ipn_articles |
| feed_id | 25 |
| feed_publisher | American Association for the Advancement of Science (AAAS) |
| feed_publisher_url | http://www.aaas.org/ |
| insertion_date | 2018-12-14 |
| journaleissn | 1095-9203 |
| journalissn | 0036-8075 |
| publikationsjahr_anzeige | 2018 |
| publikationsjahr_facette | 2018 |
| publikationsjahr_intervall | 7984:2015-2019 |
| publikationsjahr_sort | 2018 |
| publisher | American Association for the Advancement of Science (AAAS) |
| quelle | Science |
| relation | http://science.sciencemag.org/cgi/content/short/362/6420/eaat8127?rss=1 |
| schlagwort | Genetics, Online Only |
| search_space | articles |
| shingle_author_1 | 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., Moran Losada, P., 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., Psych; ENCODE Consortium, Peters, M. A., Gerstein, M., Liu, C., Iakoucheva, L. M., Pinto, D., Geschwind, D. H. |
| shingle_author_2 | 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., Moran Losada, P., 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., Psych; ENCODE Consortium, Peters, M. A., Gerstein, M., Liu, C., Iakoucheva, L. M., Pinto, D., Geschwind, D. H. |
| shingle_author_3 | 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., Moran Losada, P., 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., Psych; ENCODE Consortium, Peters, M. A., Gerstein, M., Liu, C., Iakoucheva, L. M., Pinto, D., Geschwind, D. H. |
| shingle_author_4 | 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., Moran Losada, P., 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., Psych; ENCODE Consortium, Peters, M. A., Gerstein, M., Liu, C., Iakoucheva, L. M., Pinto, D., Geschwind, D. H. |
| shingle_catch_all_1 | Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder Genetics, Online Only 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. 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., Moran Losada, P., 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., Psych; ENCODE Consortium, Peters, M. A., Gerstein, M., Liu, C., Iakoucheva, L. M., Pinto, D., Geschwind, D. H. American Association for the Advancement of Science (AAAS) 0036-8075 00368075 1095-9203 10959203 |
| shingle_catch_all_2 | Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder Genetics, Online Only 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. 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., Moran Losada, P., 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., Psych; ENCODE Consortium, Peters, M. A., Gerstein, M., Liu, C., Iakoucheva, L. M., Pinto, D., Geschwind, D. H. American Association for the Advancement of Science (AAAS) 0036-8075 00368075 1095-9203 10959203 |
| shingle_catch_all_3 | Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder Genetics, Online Only 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. 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., Moran Losada, P., 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., Psych; ENCODE Consortium, Peters, M. A., Gerstein, M., Liu, C., Iakoucheva, L. M., Pinto, D., Geschwind, D. H. American Association for the Advancement of Science (AAAS) 0036-8075 00368075 1095-9203 10959203 |
| shingle_catch_all_4 | Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder Genetics, Online Only 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. 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., Moran Losada, P., 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., Psych; ENCODE Consortium, Peters, M. A., Gerstein, M., Liu, C., Iakoucheva, L. M., Pinto, D., Geschwind, D. H. American Association for the Advancement of Science (AAAS) 0036-8075 00368075 1095-9203 10959203 |
| shingle_title_1 | Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder |
| shingle_title_2 | Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder |
| shingle_title_3 | Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder |
| shingle_title_4 | Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder |
| timestamp | 2025-06-30T23:37:40.373Z |
| titel | Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder |
| titel_suche | Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder |
| topic | W V TE-TZ SQ-SU WW-YZ TA-TD U |
| uid | ipn_articles_6369582 |