Regulatory sites for known and novel splicing in human basal ganglia are enriched for disease-relevant information
| Autor: | Pedro Quijada Leyton, Mina Ryten, Daniah Trabzuni, Andrew Thomason, John Hardy, Regina H. Reynolds, Sebastian Guelfi, Sarah A. Gagliano, Colin Smith, Adaikalavan Ramasamy, Jana Vandrovcova, Karishma D’Sa, Michael E. Weale, Kerrin S. Small, Leonoardo Collado-Torres, Mike A. Nalls, David Zhang, Juan A. Botía |
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| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
Putamen Disease Computational biology Human brain Biology Transcriptome 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure Gene expression RNA splicing Expression quantitative trait loci medicine 030217 neurology & neurosurgery 030304 developmental biology Genetic association |
| DOI: | 10.1101/591156 |
| Popis: | Genome-wide association studies have generated an increasing number of common genetic variants that affect neurological and psychiatric disease risk. Given that many causal variants are likely to operate by regulating gene expression, an improved understanding of the genetic control of gene expression in human brain is vital. However, the difficulties of sampling human brain, and its complexity, has meant that brain-related expression quantitative trait loci (eQTL) and allele specific expression (ASE) signals have been more limited in their explanatory power than might otherwise be expected. To address this, we use paired genomic and transcriptomic data from putamen and substantia nigra dissected from 117 brains, combined with a comprehensive set of analyses, to interrogate regulation at different stages of RNA processing and uncover novel transcripts. We identify disease-relevant regulatory loci and reveal the types of analyses and regulatory positions yielding the most disease-specific information. We find that splicing eQTLs are enriched for neuron-specific regulatory information; that ASE analyses provide highly cell-specific regulatory information; and that incomplete annotation of the brain transcriptome limits the interpretation of risk loci for neuropsychiatric disease. We release this rich resource of regulatory data through a searchable webserver, http://braineacv2.inf.um.es/. |
| Databáze: | OpenAIRE |
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