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Finding genetically-supported drug targets for Parkinson's disease using Mendelian randomization of the druggable genome

التفاصيل البيبلوغرافية
العنوان: Finding genetically-supported drug targets for Parkinson's disease using Mendelian randomization of the druggable genome
المؤلفون: Storm, Catherine S., Kia, Demis A., Almramhi, Mona M., Bandres-Ciga, Sara, Finan, Chris, Noyce, A. J., Kaiyrzhanov, R., Middlehurst, B., Tan, M., Houlden, Henry, Morris, H. R., Plun-Favreau, H., Holmans, Peter, Hardy, J., Trabzuni, D., Quinn, J., Bubb, Vivien, Mok, K. Y., Kinghorn, K. J., Lewis, P., Schreglmann, S. R., Lovering, R., R'Bibo, L., Manzoni, C., Rizig, M., Ryten, Mina, Guelfi, S., Escott-Price, Valentina, Chelban, Viorica, Foltynie, T., Williams, N., Morrison, K. E., Clarke, C., Harvey, K., Jacobs, B. M., Brice, Alexis, Danjou, Fabrice, Lesage, S., Corvol, Jean-Christophe, Martinez, M., Schulte, C., Brockmann, Kathrin, Simón-Sánchez, J., Heutink, Peter, Rizzu, P., Sharma, M., Gasser, T., Schneider, S. A., Cookson, Mark R, Blauwendraat, Cornelis, Craig, David W, Billingsley, K., Makarious, M. B., Narendra, D. P., Faghri, F., Gibbs, J. R., Hernandez, D. G., Van Keuren-Jensen, K., Shulman, J. M., Iwaki, H., Leonard, H. L., Nalls, M. A., Robak, L., Bras, Jose, Guerreiro, Rita, Lubbe, S., Troycoco, T., Finkbeiner, S., Mencacci, N. E., Lungu, C., Singleton, A. B., Scholz, S. W., Reed, X., Uitti, R. J., Ross, O. A., Grenn, F. P., Moore, A., Alcalay, Roy N, Wszolek, Z. K., Gan-Or, Z., Rouleau, G. A., Krohn, L., Mufti, K., van Hilten, J. J., Marinus, J., Adarmes-Gómez, A.D, Aguilar Barberà , Miquel, Alvarez, Ignacio, Alvarez, Victoria, Barrero, F. J., Yarza, J. A. B., Bernal-Bernal, I., Blázquez Estrada, Marta, Bonilla-Toribio, Marta, Botía, J. A., Boungiorno, M. T., Buiza-Rueda, Dolores, Cámara, Ana, Carrillo, F., Carrión-Claro, M., Cerdan, Debora, Clarimón, Jordi, Compta, Yaroslau, Diez-Fairen, M., Dols Icardo, Oriol, Duarte, Jacinto, Duran, Raquel, Escamilla-Sevilla, Francisco, Ezquerra, Mario, Feliz, Cici, Fernández, Manel, Fernández-Santiago, Rubén, Garcia, C., García-Ruiz, Pedro, Gómez-Garre, P., Gomez Heredia, Maria Jose, Gonzalez-Aramburu, Isabel, Pagola, A. G., Hoenicka, Janet, Infante, Jon, Jesús, S., Jiménez-Escrig, Adriano, Kulisevsky, Jaime, Labrador-Espinosa, Miguel A, Lopez-Sendon, Jose Luis, de Munain Arregui, A. L., Macías-García, Daniel, Torres, I. M., Marín, Juan, Marti, Maria Jose, Martínez-Castrillo, Juan Carlos, Méndez-del-Barrio, C., González, M. M., Mata, Marina, Mínguez, A., Mir, P., Rezola, E. M., Muñoz, Esteban, Pagonabarraga Mora, Javier, Pastor, Pau, Perez-Errazquin, Francisco, Periñán-Tocino, T., Ruiz-Martínez, J., Ruz, Clara, Rodriguez, A. S., Sierra, Maria, Suarez-Sanmartin, E., Tabernero, Cesar, Tartari, J. P., Tejera-Parrado, C., Tolosa, Eduard, Valldeoriola, Francesc, Vargas-González, L., Vela, Lydia, Vives, Francisco, Zimprich, Alexander, Pihlstrom, L., Toft, M., Taba, P., Koks, S., Hassin-Baer, S., Majamaa, K., Siitonen, A., Tienari, P., Okubadejo, N. U., Ojo, O. O., Shashkin, C., Zharkinbekova, N., Akhmetzhanov, V., Kaishybayeva, G., Karimova, A., Khaibullin, T., Lynch, T. L., Hingorani, Aroon, Wood, Nicholas W., Universitat Autònoma de Barcelona
سنة النشر: 2021
المجموعة: Universitat Autònoma de Barcelona: Dipòsit Digital de Documents de la UAB
مصطلحات موضوعية: Brain, Case-Control Studies, Cohort Studies, Disease Progression, Gene Expression Regulation, Genetic Predisposition to Disease, Genetic Variation, Genome, Human, Humans, Mendelian Randomization Analysis, Parkinson Disease, Quantitative Trait Loci, Risk Factors
الوصف: Parkinson's disease is a neurodegenerative movement disorder that currently has no disease-modifying treatment, partly owing to inefficiencies in drug target identification and validation. We use Mendelian randomization to investigate over 3,000 genes that encode druggable proteins and predict their efficacy as drug targets for Parkinson's disease. We use expression and protein quantitative trait loci to mimic exposure to medications, and we examine the causal effect on Parkinson's disease risk (in two large cohorts), age at onset and progression. We propose 23 drug-targeting mechanisms for Parkinson's disease, including four possible drug repurposing opportunities and two drugs which may increase Parkinson's disease risk. Of these, we put forward six drug targets with the strongest Mendelian randomization evidence. There is remarkably little overlap between our drug targets to reduce Parkinson's disease risk versus progression, suggesting different molecular mechanisms. Drugs with genetic support are considerably more likely to succeed in clinical trials, and we provide compelling genetic evidence and an analysis pipeline to prioritise Parkinson's disease drug development.
نوع الوثيقة: article in journal/newspaper
وصف الملف: application/pdf
اللغة: English
تدمد: 20411723
العلاقة: Nature communications; Vol. 12 Núm. 1 (december 2021), p. 7342; https://ddd.uab.cat/record/264453Test; urn:10.1038/s41467-021-26280-1; urn:oai:ddd.uab.cat:264453; urn:scopus_id:85121559630; urn:pmid:34930919; urn:articleid:20411723v12n1p7342; urn:pmc-uid:8688480; urn:pmcid:PMC8688480; urn:oai:pubmedcentral.nih.gov:8688480; urn:oai:egreta.uab.cat:publications/426a8b4f-45a1-4552-a802-00b4bd33edfc
الإتاحة: https://ddd.uab.cat/record/264453Test
حقوق: open access ; Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. ; https://creativecommons.org/licenses/by/4.0Test/
رقم الانضمام: edsbas.23E1B62D
قاعدة البيانات: BASE
الوصف
تدمد:20411723