Genome-wide Association and Meta-analysis of Age-at-Onset in Parkinson Disease: Evidence From COURAGE-PD Consortium 10.1212/WNL.0000000000200699

Autor: Grover, Sandeep, Ashwin, Ashok Kumar Sreelatha, Pihlstrom, Lasse, Domenighetti, Cloé, Schulte, Claudia, Sugier, Pierre-Emmanuel, Radivojkov-Blagojevic, Milena, Lichtner, Peter, Mohamed, Océane, Portugal, Berta, Landoulsi, Zied, May, Patrick, Bobbili, Dheeraj Reddy, Edsall, Connor, Bartusch, Felix, Hanussek, Maximilian, Krüger, Jens, Hernandez, Dena G., Blauwendraat, Cornelis, Mellick, George D., Zimprich, Alexander, Pirker, Walter, Tan, Manuela, Rogaeva, Ekaterina, Lang, Anthony, Koks, Sulev, Taba, Pille, Lesage, Suzanne, Brice, Alexis, Corvol, Jean-Christophe, Chartier-Harlin, Marie-Christine, Mutez, Eugenie, Brockmann, Kathrin, Deutschländer, Angela B., Hadjigeorgiou, Georges M., Dardiotis, Efthimos, Stefanis, Leonidas, Simitsi, Athina Maria, Valente, Enza Maria, Petrucci, Simona, Straniero, Letizia, Zecchinelli, Anna, Pezzoli, Gianni, Brighina, Laura, Ferrarese, Carlo, Annesi, Grazia, Quattrone, Andrea, Gagliardi, Monica, Burbulla, Lena F., Matsuo, Hirotaka, Kawamura, Yusuke, Hattori, Nobutaka, Nishioka, Kenya, Chung, Sun Ju, Kim, Yun Joong, Pavelka, Lukas, van de Warrenburg, Bart P. C., Bloem, Bastiaan R., Singleton, Andrew B., Aasly, Jan, Toft, Mathias, Guedes, Leonor Correia, Ferreira, Joaquim J., Bardien, Soraya, Carr, Jonathan, Tolosa, Eduardo, Ezquerra, Mario, Pastor, Pau, Diez-Fairen, Monica, Wirdefeldt, Karin, Pedersen, Nancy L., Ran, Caroline, Belin, Andrea C., Puschmann, Andreas, Hellberg, Clara, Clarke, Carl E., Morrison, Karen E., Krainc, Dimitri, Farrer, Matt J., Krüger, Rejko, Elbaz, Alexis, Gasser, Thomas, Sharma, Manu, of, On Behalf, Genetics, The Comprehensive Unbiased Risk Factor Assessment For, consortium, Environment In Parkinson Textquoterights Disease Courage-P. D.
Přispěvatelé: Fonds National de la Recherche - FnR [sponsor], Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group) [research center]
Jazyk: angličtina
Rok vydání: 2022
Předmět:
ISSN: 3431-1866
Popis: Background and Objectives: Considerable heterogeneity exists in the literature concerning genetic determinants of the age of onset (AAO) of Parkinson\textquoterights disease (PD), which could be attributed to lack of well-powered replication cohorts. The previous largest GWAS identified SNCA and TMEM175 loci on chromosome (Chr) 4 with a significant influence on AAO of PD, these have not been independently replicated. The present study aims to conduct a meta-analysis of GWAS of PD AAO and validate previously observed findings in worldwide populations.Methods: A meta-analysis was performed on PD AAO GWAS of 30 populations of predominantly European ancestry from the Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson\textquoterights Disease (COURAGE-PD) consortium. This was followed up by combining our study with the largest publicly available European ancestry dataset compiled by the International Parkinson disease Genomics Consortium (IPDGC).Results: The COURAGE-PD included a cohort of 8,535 patients with PD (91.9\%: Europeans, 9.1\%: East-Asians). The average AAO in the COURAGE-PD dataset was 58.9 years (SD=11.6), with an under-representation of females (40.2\%). The heritability estimate for AAO in COURAGE-PD was 0.083 (SE=0.057). None of the loci reached genome-wide significance (P\
Databáze: OpenAIRE