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

• DOI: 10.1038/s41467-020-14483-x
• Publication Date: 2020-02-25T11:03:07Z
• Authors: Sebastian Guelfi; Karishma D’Sa; Juan A. Botía; Jana Vandrovcova; Regina H. Reynolds; David Zhang; Daniah Trabzuni; Leonardo Collado-...; Andrew Thomason; Pedro Quijada Leyton; Sarah A. Gagliano...; Mike A. Nalls; ; Alastair J. Noyce; Aude Nicolas; Mark R. Cookson; Sara Bandres-Ciga; J. Raphael Gibbs; Dena G. Hernandez; Andrew B. Singleton; Xylena Reed; Hampton Leonard; Cornelis Blauwend...; Faraz Faghri; Jose Bras; Rita Guerreiro; Arianna Tucci; Demis A. Kia; Henry Houlden; Helene Plun-Favreau; Kin Y Mok; Nicholas W. Wood; Ruth Lovering; Lea R’Bibo; Mie Rizig; Viorica Chelban; Manuela Tan; Huw R. Morris; Ben Middlehurst; John Quinn; Kimberley Billing...; Peter Holmans; Kerri J. Kinghorn; Patrick Lewis; Valentina Escott-...; Nigel Williams; Thomas Foltynie; Alexis Brice; Fabrice Danjou; Suzanne Lesage; Jean-Christophe C...; Maria Martinez; Anamika Giri; Claudia Schulte; Kathrin Brockmann; Javier Simón-Sánchez; Peter Heutink; Thomas Gasser; Patrizia Rizzu; Manu Sharma; Joshua M. Shulman; Laurie Robak; Steven Lubbe; Niccolo E. Mencacci; Steven Finkbeiner; Codrin Lungu; Sonja W. Scholz; Ziv Gan-Or; Guy A. Rouleau; Lynne Krohan; Jacobus J. van Hi...; Johan Marinus; Astrid D. Adarmes...; Inmaculada Bernal...; Marta Bonilla-Tor...; Dolores Buiza-Rueda; Fátima Carrillo; Mario Carrión-Claro; Pablo Mir; Pilar Gómez-Garre; Silvia Jesús; Miguel A. Labrado...; Daniel Macias; Laura Vargas-Gonz...; Carlota Méndez-de...; Teresa Periñán-To...; Cristina Tejera-P...; Monica Diez-Fairen; Miquel Aguilar; Ignacio Alvarez; María Teresa Boun...; Maria Carcel; Pau Pastor; Juan Pablo Tartari; Victoria Alvarez; Manuel Menéndez G...; Marta Blazquez; Ciara Garcia; Esther Suarez-San...; Francisco Javier ...; Elisabet Mondrago...; Jesús Alberto Ber...; Ana Gorostidi Pagola; Adolfo López de M...; Javier Ruiz-Martínez; Debora Cerdan; Jacinto Duarte; Jordi Clarimón; Oriol Dols-Icardo; Jon Infante; Juan Marín; Jaime Kulisevsky; Javier Pagonabarraga; Isabel Gonzalez-A...; Antonio Sanchez R...; María Sierra; Raquel Duran; Clara Ruz; Francisco Vives; Francisco Escamil...; Adolfo Mínguez; Ana Cámara; Yaroslau Compta; Mario Ezquerra; Maria Jose Marti; Manel Fernández; Esteban Muñoz; Rubén Fernández-S...; Eduard Tolosa; Francesc Valldeor...; Pedro García-Ruiz; Maria Jose Gomez ...; Francisco Perez E...; Janet Hoenicka; Adriano Jimenez-E...; Juan Carlos Martí...; Jose Luis Lopez-S...; Irene Martínez To...; Cesar Tabernero; Lydia Vela; Alexander Zimprich; Lasse Pihlstrom; Sulev Koks; Pille Taba; Kari Majamaa; Ari Siitonen; Njideka U. Okubadejo; Oluwadamilola O. Ojo; ; Paola Forabosco; Robert Walker; Kerrin S. Small; Colin Smith; Adaikalavan Ramasamy; John Hardy; Michael E. Weale; Mina Ryten
• Keywords: Genome-wide Association Study

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