Genome-wide landscape of RNA-binding protein target site dysregulation reveals a major impact on psychiatric disorder risk
| العنوان: | Genome-wide landscape of RNA-binding protein target site dysregulation reveals a major impact on psychiatric disorder risk |
|---|---|
| المؤلفون: | Robert B. Darnell, Olga G. Troyanskaya, Kathleen M. Chen, Christopher Y. Park, Jian Zhou, Aaron K. Wong, Chandra L. Theesfeld |
| المصدر: | Nature genetics |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | endocrine system, medicine.medical_specialty, Quantitative Trait Loci, Cellular homeostasis, RNA-binding protein, Quantitative trait locus, Biology, Polymorphism, Single Nucleotide, Genome, Article, 03 medical and health sciences, Deep Learning, 0302 clinical medicine, Gene Frequency, Genetics, medicine, Humans, Coding region, Genetic Predisposition to Disease, RNA Processing, Post-Transcriptional, Nuclear Factor 90 Proteins, Psychiatry, 3' Untranslated Regions, Ribonucleoprotein, U5 Small Nuclear, 030304 developmental biology, 0303 health sciences, Mental Disorders, RNA-Binding Proteins, Translation (biology), Peptide Elongation Factors, medicine.disease, Gene Expression Regulation, Phospholipases, Schizophrenia, Mutation, RNA splicing, Trans-Activators, RNA Helicases, 030217 neurology & neurosurgery, Genome-Wide Association Study |
| الوصف: | Despite the strong genetic basis of psychiatric disorders, the underlying molecular mechanisms are largely unmapped. RNA-binding proteins (RBPs) are responsible for most post-transcriptional regulation, from splicing to translation to localization. RBPs thus act as key gatekeepers of cellular homeostasis, especially in the brain. However, quantifying the pathogenic contribution of noncoding variants impacting RBP target sites is challenging. Here, we leverage a deep learning approach that can accurately predict the RBP target site dysregulation effects of mutations and discover that RBP dysregulation is a principal contributor to psychiatric disorder risk. RBP dysregulation explains a substantial amount of heritability not captured by large-scale molecular quantitative trait loci studies and has a stronger impact than common coding region variants. We share the genome-wide profiles of RBP dysregulation, which we use to identify DDHD2 as a candidate schizophrenia risk gene. This resource provides a new analytical framework to connect the full range of RNA regulation to complex disease. |
| تدمد: | 1546-1718 1061-4036 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c04b221d281dd1cdbce03593e9128d03 https://doi.org/10.1038/s41588-020-00761-3 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....c04b221d281dd1cdbce03593e9128d03 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 15461718 10614036 |
|---|