Regulatory sites for splicing in human basal ganglia are enriched for disease-relevant information.
Alleles
Gene Expression Regulation
Genome-Wide Association Study
Humans
Nervous System Diseases
/ genetics
Neurons
/ physiology
Parkinson Disease
/ genetics
Polymorphism, Single Nucleotide
Putamen
/ physiology
Quantitative Trait Loci
RNA Splicing
Reproducibility of Results
Schizophrenia
/ genetics
Substantia Nigra
/ physiology
Transcriptome
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
25 02 2020
25 02 2020
Historique:
received:
05
04
2019
accepted:
20
12
2019
entrez:
27
2
2020
pubmed:
27
2
2020
medline:
23
5
2020
Statut:
epublish
Résumé
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/.
Identifiants
pubmed: 32098967
doi: 10.1038/s41467-020-14483-x
pii: 10.1038/s41467-020-14483-x
pmc: PMC7042265
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1041Subventions
Organisme : Medical Research Council
ID : MR/K01417X/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L010305/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0801418
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/T04604X/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N026004/1
Pays : United Kingdom
Organisme : RCUK | Medical Research Council (MRC)
ID : MR/N008324/1
Pays : International
Organisme : Medical Research Council
ID : MR/S006753/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P005748/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L023784/2
Pays : United Kingdom
Investigateurs
Alastair J Noyce
(AJ)
Aude Nicolas
(A)
Mark R Cookson
(MR)
Sara Bandres-Ciga
(S)
J Raphael Gibbs
(JR)
Dena G Hernandez
(DG)
Andrew B Singleton
(AB)
Xylena Reed
(X)
Hampton Leonard
(H)
Cornelis Blauwendraat
(C)
Faraz Faghri
(F)
Jose Bras
(J)
Rita Guerreiro
(R)
Arianna Tucci
(A)
Demis A Kia
(DA)
Henry Houlden
(H)
Helene Plun-Favreau
(H)
Kin Y Mok
(KY)
Nicholas W Wood
(NW)
Ruth Lovering
(R)
Lea R'Bibo
(L)
Mie Rizig
(M)
Viorica Chelban
(V)
Manuela Tan
(M)
Huw R Morris
(HR)
Ben Middlehurst
(B)
John Quinn
(J)
Kimberley Billingsley
(K)
Peter Holmans
(P)
Kerri J Kinghorn
(KJ)
Patrick Lewis
(P)
Valentina Escott-Price
(V)
Nigel Williams
(N)
Thomas Foltynie
(T)
Alexis Brice
(A)
Fabrice Danjou
(F)
Suzanne Lesage
(S)
Jean-Christophe Corvol
(JC)
Maria Martinez
(M)
Anamika Giri
(A)
Claudia Schulte
(C)
Kathrin Brockmann
(K)
Javier Simón-Sánchez
(J)
Peter Heutink
(P)
Thomas Gasser
(T)
Patrizia Rizzu
(P)
Manu Sharma
(M)
Joshua M Shulman
(JM)
Laurie Robak
(L)
Steven Lubbe
(S)
Niccolo E Mencacci
(NE)
Steven Finkbeiner
(S)
Codrin Lungu
(C)
Sonja W Scholz
(SW)
Ziv Gan-Or
(Z)
Guy A Rouleau
(GA)
Lynne Krohan
(L)
Jacobus J van Hilten
(JJ)
Johan Marinus
(J)
Astrid D Adarmes-Gómez
(AD)
Inmaculada Bernal-Bernal
(I)
Marta Bonilla-Toribio
(M)
Dolores Buiza-Rueda
(D)
Fátima Carrillo
(F)
Mario Carrión-Claro
(M)
Pablo Mir
(P)
Pilar Gómez-Garre
(P)
Silvia Jesús
(S)
Miguel A Labrador-Espinosa
(MA)
Daniel Macias
(D)
Laura Vargas-González
(L)
Carlota Méndez-Del-Barrio
(C)
Teresa Periñán-Tocino
(T)
Cristina Tejera-Parrado
(C)
Monica Diez-Fairen
(M)
Miquel Aguilar
(M)
Ignacio Alvarez
(I)
María Teresa Boungiorno
(MT)
Maria Carcel
(M)
Pau Pastor
(P)
Juan Pablo Tartari
(JP)
Victoria Alvarez
(V)
Manuel Menéndez González
(MM)
Marta Blazquez
(M)
Ciara Garcia
(C)
Esther Suarez-Sanmartin
(E)
Francisco Javier Barrero
(FJ)
Elisabet Mondragon Rezola
(EM)
Jesús Alberto Bergareche Yarza
(JAB)
Ana Gorostidi Pagola
(AG)
Adolfo López de Munain Arregui
(ALM)
Javier Ruiz-Martínez
(J)
Debora Cerdan
(D)
Jacinto Duarte
(J)
Jordi Clarimón
(J)
Oriol Dols-Icardo
(O)
Jon Infante
(J)
Juan Marín
(J)
Jaime Kulisevsky
(J)
Javier Pagonabarraga
(J)
Isabel Gonzalez-Aramburu
(I)
Antonio Sanchez Rodriguez
(AS)
María Sierra
(M)
Raquel Duran
(R)
Clara Ruz
(C)
Francisco Vives
(F)
Francisco Escamilla-Sevilla
(F)
Adolfo Mínguez
(A)
Ana Cámara
(A)
Yaroslau Compta
(Y)
Mario Ezquerra
(M)
Maria Jose Marti
(MJ)
Manel Fernández
(M)
Esteban Muñoz
(E)
Rubén Fernández-Santiago
(R)
Eduard Tolosa
(E)
Francesc Valldeoriola
(F)
Pedro García-Ruiz
(P)
Maria Jose Gomez Heredia
(MJG)
Francisco Perez Errazquin
(FP)
Janet Hoenicka
(J)
Adriano Jimenez-Escrig
(A)
Juan Carlos Martínez-Castrillo
(JC)
Jose Luis Lopez-Sendon
(JL)
Irene Martínez Torres
(IM)
Cesar Tabernero
(C)
Lydia Vela
(L)
Alexander Zimprich
(A)
Lasse Pihlstrom
(L)
Sulev Koks
(S)
Pille Taba
(P)
Kari Majamaa
(K)
Ari Siitonen
(A)
Njideka U Okubadejo
(NU)
Oluwadamilola O Ojo
(OO)
Paola Forabosco
(P)
Robert Walker
(R)
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