RT Journal Article
T1 Regulatory sites for splicing in human basal ganglia are enriched for disease-relevant information.
A1 Guelfi, Sebastian
A1 D'Sa, Karishma
A1 Botía, Juan A
A1 Vandrovcova, Jana
A1 Reynolds, Regina H
A1 Zhang, David
A1 Trabzuni, Daniah
A1 Collado-Torres, Leonardo
A1 Thomason, Andrew
A1 Quijada Leyton, Pedro
A1 Gagliano Taliun, Sarah A
A1 Nalls, Mike A
A1 International Parkinson’s Disease Genomics Consortium (IPDGC), 
A1 UK Brain Expression Consortium (UKBEC), 
A1 Small, Kerrin S
A1 Smith, Colin
A1 Ramasamy, Adaikalavan
A1 Hardy, John
A1 Weale, Michael E
A1 Ryten, Mina
AB 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/.
YR 2020
FD 2020-02-25
LK https://hdl.handle.net/10668/26229
UL https://hdl.handle.net/10668/26229
LA en
DS RISalud
RD Apr 17, 2025