التفاصيل البيبلوغرافية
| العنوان: |
Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies. |
| المؤلفون: |
Nalls, Mike A, Blauwendraat, Cornelis, Bras, Jose, Foltynie, Thomas, Gan-Or, Ziv, Garcia, Ciara, García-Ruiz, Pedro, Gibbs, J Raphael, Gomez Heredia, Maria Jose, Gómez-Garre, Pilar, González, Manuel Menéndez, Gonzalez-Aramburu, Isabel, Guelfi, Sebastian, Young, Emily, Guerreiro, Rita, Hardy, John, Hassin-Baer, Sharon, Hernandez, Dena G, Hoenicka, Janet, Holmans, Peter, Houlden, Henry, Infante, Jon, Iwaki, Hirotaka, Jesús, Silvia, von Coelln, Rainer, Jimenez-Escrig, Adriano, Kaishybayeva, Gulnaz, Kaiyrzhanov, Rauan, Karimova, Altynay, Kia, Demis A, Kinghorn, Kerri J, Koks, Sulev, Krohn, Lynne, Kulisevsky, Jaime, Labrador-Espinosa, Miguel A, Simon Sanchez, Javier, Leonard, Hampton L, Lesage, Suzanne, Lewis, Patrick, Lopez-Sendon, Jose Luis, Lovering, Ruth, Lubbe, Steven, Lungu, Codrin, Macias, Daniel, Majamaa, Kari, Manzoni, Claudia, Schulte, Claudia, Marín, Juan, Marinus, Johan, Marti, Maria Jose, Martinez, Maria, Martínez Torres, Irene, Martínez-Castrillo, Juan Carlos, Mata, Marina, Mencacci, Niccolo E, Méndez-Del-Barrio, Carlota, Middlehurst, Ben, Sharma, Manu, Mínguez, Adolfo, Mir, Pablo, Mok, Kin Y, Morris, Huw R, Muñoz, Esteban, Narendra, Derek, Noyce, Alastair J, Ojo, Oluwadamilola O, Okubadejo, Njideka U, Pagola, Ana Gorostidi, Pastor, Pau, Perez Errazquin, Francisco, Periñán-Tocino, Teresa, Pihlstrom, Lasse, Plun-Favreau, Helene, Quinn, John, R'Bibo, Lea, Reed, Xylena, Rezola, Elisabet Mondragon, Pihlstrøm, Lasse, Rizig, Mie, Rizzu, Patrizia, Robak, Laurie, Rodriguez, Antonio Sanchez, Rouleau, Guy A, Ruiz-Martínez, Javier, Ruz, Clara, Ryten, Mina, Sadykova, Dinara, Scholz, Sonja W, Siitonen, Ari, Schreglmann, Sebastian, Shashkin, Chingiz, Shulman, Joshua M, Sierra, María, Singleton, Andrew B, Suarez-Sanmartin, Esther, Taba, Pille, Tabernero, Cesar, Tan, Manuela X, Tartari, Juan Pablo, Tejera-Parrado, Cristina, Toft, Mathias, Tolosa, Eduard, Trabzuni, Daniah, Valldeoriola, Francesc, van Hilten, Jacobus J, Van Keuren-Jensen, Kendall, Vallerga, Costanza L, Leonard, Hampton, Vargas-González, Laura, Vela, Lydia, Vives, Francisco, Williams, Nigel, Wood, Nicholas W, Zharkinbekova, Nazira, Zharmukhanov, Zharkyn, Zholdybayeva, Elena, Zimprich, Alexander, Ylikotila, Pauli, Faghri, Faraz, Shulman, Lisa M, Reich, Stephen, Savitt, Joseph, Agee, Michelle, Alipanahi, Babak, Auton, Adam, Bell, Robert K, Bryc, Katarzyna, Elson, Sarah L, Fontanillas, Pierre, Furlotte, Nicholas A, Huber, Karen E, Hicks, Barry, Jewett, Ethan M, Jiang, Yunxuan, Kleinman, Aaron, Lin, Keng-Han, Litterman, Nadia K, McCreight, Jennifer C, McIntyre, Matthew H, McManus, Kimberly F, Mountain, Joanna L, Noblin, Elizabeth S, Northover, Carrie A M, Pitts, Steven J, Poznik, G David, Sathirapongsasuti, J Fah, Shelton, Janie F, Shringarpure, Suyash, Tian, Chao, Tung, Joyce, Vacic, Vladimir, Wang, Xin, Wilson, Catherine H, Anderson, Tim, Bentley, Steven, Dalrymple-Alford, John, Fowdar, Javed, Gratten, Jacob, Botia, Juan A, Halliday, Glenda, Henders, Anjali K, Hickie, Ian, Kassam, Irfahan, Kennedy, Martin, Kwok, John, Lewis, Simon, Mellick, George, Montgomery, Grant, Pearson, John, Pitcher, Toni, Sidorenko, Julia, Silburn, Peter A, Visscher, Peter M, Wallace, Leanne, Wray, Naomi R, Xue, Angli, Yang, Jian, Zhang, Futao, Corvol, Jean-Christophe, Jankovic, Joseph, Heilbron, Karl, Sutherland, Margaret, Tienari, Pentti, Andreassen, Ole A, Bangale, Tushar, Brice, Alexis, Bandres-Ciga, Sara, Gasser, Thomas, Heutink, Peter, Hinds, David A, Hardy, John A, Graham, Robert R, Chang, Diana, Team, 23andMe Research, Consortium, System Genomics of Parkinson's Disease, Consortium, International Parkinson's Disease Genomics, Adarmes-Gómez, Astrid D, Aguilar, Miquel, Aitkulova, Akbota, Akhmetzhanov, Vadim, Alcalay, Roy N, Alvarez, Ignacio, Tan, Manuela, Alvarez, Victoria, Barrero, Francisco Javier, Bergareche Yarza, Jesús Alberto, Bernal-Bernal, Inmaculada, Billingsley, Kimberley, Blazquez, Marta, Bonilla-Toribio, Marta, Botía, Juan A, Boungiorno, María Teresa, Brockmann, Kathrin, Bubb, Vivien, Buiza-Rueda, Dolores, Cámara, Ana, Carrillo, Fátima, Carrión-Claro, Mario, Cerdan, Debora, Chelban, Viorica, Clarimón, Jordi, Clarke, Carl, Compta, Yaroslau, Cookson, Mark R, Craig, David W, Danjou, Fabrice, Diez-Fairen, Monica, Dols-Icardo, Oriol, Duarte, Jacinto, Duran, Raquel, Escamilla-Sevilla, Francisco, Escott-Price, Valentina, Ezquerra, Mario, Feliz, Cici, Fernández, Manel, Fernández-Santiago, Rubén, Finkbeiner, Steven |
| المصدر: |
The lancet / Neurology 18(12), 1091-1102 (2019). doi:10.1016/S1474-4422(19)30320-5 |
| بيانات النشر: |
Lancet Publ. Group |
| سنة النشر: |
2019 |
| مصطلحات موضوعية: |
info:eu-repo/classification/ddc/610, Databases, Genetic, Genetic Loci: genetics, Genetic Predisposition to Disease: epidemiology, Genetic Predisposition to Disease: genetics, Genome-Wide Association Study: methods, Humans, Parkinson Disease: diagnosis, Parkinson Disease: epidemiology, Parkinson Disease: genetics, Risk Factors |
| جغرافية الموضوع: |
DE |
| الوصف: |
Genome-wide association studies (GWAS) in Parkinson's disease have increased the scope of biological knowledge about the disease over the past decade. We aimed to use the largest aggregate of GWAS data to identify novel risk loci and gain further insight into the causes of Parkinson's disease.We did a meta-analysis of 17 datasets from Parkinson's disease GWAS available from European ancestry samples to nominate novel loci for disease risk. These datasets incorporated all available data. We then used these data to estimate heritable risk and develop predictive models of this heritability. We also used large gene expression and methylation resources to examine possible functional consequences as well as tissue, cell type, and biological pathway enrichments for the identified risk factors. Additionally, we examined shared genetic risk between Parkinson's disease and other phenotypes of interest via genetic correlations followed by Mendelian randomisation.Between Oct 1, 2017, and Aug 9, 2018, we analysed 7·8 million single nucleotide polymorphisms in 37 688 cases, 18 618 UK Biobank proxy-cases (ie, individuals who do not have Parkinson's disease but have a first degree relative that does), and 1·4 million controls. We identified 90 independent genome-wide significant risk signals across 78 genomic regions, including 38 novel independent risk signals in 37 loci. These 90 variants explained 16-36% of the heritable risk of Parkinson's disease depending on prevalence. Integrating methylation and expression data within a Mendelian randomisation framework identified putatively associated genes at 70 risk signals underlying GWAS loci for follow-up functional studies. Tissue-specific expression enrichment analyses suggested Parkinson's disease loci were heavily brain-enriched, with specific neuronal cell types being implicated from single cell data. We found significant genetic correlations with brain volumes (false discovery rate-adjusted p=0·0035 for intracranial volume, p=0·024 for putamen volume), smoking status ... |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| العلاقة: |
info:eu-repo/semantics/altIdentifier/issn/1474-4465; info:eu-repo/semantics/altIdentifier/pmid/pmid:31701892; info:eu-repo/semantics/altIdentifier/issn/1474-4422; https://pub.dzne.de/record/141624Test; https://pub.dzne.de/search?p=id:%22DZNE-2020-07948%22Test |
| الإتاحة: |
https://doi.org/10.1016/S1474-4422Test(19)30320-5
https://pub.dzne.de/record/141624Test
https://pub.dzne.de/search?p=id:%22DZNE-2020-07948%22Test |
| حقوق: |
info:eu-repo/semantics/closedAccess |
| رقم الانضمام: |
edsbas.762A12FE |
| قاعدة البيانات: |
BASE |
