Regulatory sites for splicing in human basal ganglia are enriched for disease-relevant information

Sebastian Guelfi, Karishma D’Sa, Juan A. Botía, Jana Vandrovcova, Regina H. Reynolds, David Zhang, Daniah Trabzuni, Leonardo Collado-Torres, Andrew Thomason, Pedro Quijada Leyton, Sarah A. Gagliano Taliun, Mike A. Nalls, Kerrin S. Small, Colin Smith, Adaikalavan Ramasamy, John Hardy, Michael E. Weale and Mina Ryten ()
Additional contact information
Sebastian Guelfi: University College London (UCL) Institute of Neurology
Karishma D’Sa: University College London (UCL) Institute of Neurology
Juan A. Botía: University College London (UCL) Institute of Neurology
Jana Vandrovcova: University College London (UCL) Institute of Neurology
Regina H. Reynolds: University College London (UCL) Institute of Neurology
David Zhang: University College London (UCL) Institute of Neurology
Daniah Trabzuni: University College London (UCL) Institute of Neurology
Leonardo Collado-Torres: Lieber Institute for Brain Development
Andrew Thomason: Goldsmiths, University of London, New Cross
Pedro Quijada Leyton: Goldsmiths, University of London, New Cross
Sarah A. Gagliano Taliun: Center for Statistical Genetics, University of Michigan
Mike A. Nalls: Laboratory of Neurogenetics, National Institute on Aging, US National Institutes of Health
Kerrin S. Small: Department of Twin Research and Genetic Epidemiology, King’s College London
Colin Smith: University of Edinburgh
Adaikalavan Ramasamy: University College London (UCL) Institute of Neurology
John Hardy: University College London (UCL) Institute of Neurology
Michael E. Weale: School of Medical Sciences, King’s College London, Guy’s Hospital
Mina Ryten: University College London (UCL) Institute of Neurology

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: Abstract Genome-wide association studies have generated an increasing number of common genetic variants associated with neurological and psychiatric disease risk. An improved understanding of the genetic control of gene expression in human brain is vital considering this is the likely modus operandum for many causal variants. However, human brain sampling complexities limit the explanatory power of brain-related expression quantitative trait loci (eQTL) and allele-specific expression (ASE) signals. We address this, using paired genomic and transcriptomic data from putamen and substantia nigra from 117 human brains, interrogating regulation at different RNA processing stages and uncovering novel transcripts. We identify disease-relevant regulatory loci, find that splicing eQTLs are enriched for regulatory information of neuron-specific genes, that ASEs provide cell-specific regulatory information with evidence for cellular specificity, and that incomplete annotation of the brain transcriptome limits interpretation of risk loci for neuropsychiatric disease. This resource of regulatory data is accessible through our web server, http://braineacv2.inf.um.es/.

Date: 2020
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-020-14483-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14483-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-14483-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().