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Lookup NU author(s): Professor Camille CarrollORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply. Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations.
Author(s): Kim JJ, Vitale D, Otani DV, Lian MM, Heilbron K, Aslibekyan S, Auton A, Babalola E, Bell RK, Bielenberg J, Bryc K, Bullis E, Cannon P, Coker D, Partida GC, Dhamija D, Das S, Elson SL, Eriksson N, Filshtein T, Fitch A, Fletez-Brant K, Fontanillas P, Freyman W, Granka JM, Hernandez A, Hicks B, Hinds DA, Jewett EM, Jiang Y, Kukar K, Kwong A, Lin K-H, Llamas BA, Lowe M, McCreight JC, McIntyre MH, Micheletti SJ, Moreno ME, Nandakumar P, Nguyen DT, Noblin ES, O'Connell J, Petrakovitz AA, Poznik GD, Reynoso A, Schloetter M, Schumacher M, Shastri AJ, Shelton JF, Shi J, Shringarpure S, Su QJ, Tat SA, Tchakoute CT, Tran V, Tung JY, Wang X, Wang W, Weldon CH, Wilton P, Wong CD, Iwaki H, Lake J, Solsberg CW, Leonard H, Makarious MB, Tan E-K, Singleton AB, Bandres-Ciga S, Noyce AJ, Gatto EM, Kauffman M, Khachatryan S, Tavadyan Z, Shepherd CE, Hunter J, Kumar K, Ellis M, Renteria ME, Koks S, Zimprich A, Schumacher-Schuh AF, Rieder C, Awad PS, Tumas V, Camargos S, Fon EA, Monchi O, Fon T, Galleguillos BP, Miranda M, Bustamante ML, Olguin P, Chana P, Tang B, Shang H, Guo J, Chan P, Luo W, Arboleda G, Orozc J, del Rio MJ, Hernandez A, Salama M, Kamel WA, Zewde YZ, Brice A, Corvol J-C, Westenberger A, Illarionova A, Mollenhauer B, Klein C, Vollstedt E-J, Hopfner F, Hoglinger G, Madoev H, Trinh J, Junker J, Lohmann K, Lange LM, Sharma M, Groppa S, Gasser T, Fang Z-H, Akpalu A, Xiromerisiou G, Hadjigorgiou G, Dagklis I, Tarnanas I, Stefanis L, Stamelou M, Dadiotis E, Medina A, Chan GH-F, Ip N, Cheung NY-F, Chan P, Zhou X, Kishore A, Divya KP, Pal P, Kukkle PL, Rajan R, Borgohain R, Salari M, Quattrone A, Valente EM, Parnetti L, Avenali M, Schirinzi T, Funayama M, Hattori N, Shiraishi T, Karimova A, Kaishibayeva G, Shambetova C, Kruger R, Tan AH, Ahmad-Annuar A, Norlinah MI, Murad NAA, Azmin S, Lim S-Y, Mohamed W, Tay YW, Martinez-Ramirez D, Rodriguez-Violante M, Reyes-Perez P, Tserensodnom B, Ojha R, Anderson TJ, Pitcher TL, Sanyaolu A, Okubadejo N, Ojo O, Aasly JO, Pihlstrom L, Tan M, Ur-Rehman S, Veliz-Otani D, Cornejo-Olivas M, Doquenia ML, Rosales R, Vinuela A, Iakovenko E, Mubarak BA, Umair M, Amod F, Carr J, Bardien S, Jeon B, Kim YJ, Cubo E, Alvarez I, Hoenicka J, Beyer K, Perinan MT, Pastor P, El-Sadig S, Brolin K, Zweier C, Tinkhauser G, Krack P, Lin C-H, Wu H-C, Kung P-J, Wu R-M, Wu Y, Amouri R, Sassi SB, Basak AN, Genc G, Cakmak OO, Ertan S, Martinez-Carrasco A, Schrag A, Schapira A, Carroll C, Bale C, Grosset D, Stafford EJ, Houlden H, Morris HR, Hardy J, Mok KY, Rizig M, Wood N, Williams N, Okunoye O, Lewis PA, Kaiyrzhanov R, Weil R, Love S, Stott S, Jasaityte S, Dey S, Obese V, Espay A, O'Grady A, Sobering AK, Siddiqi B, Casey B, Fiske B, Jonas C, Cruchaga C, Pantazis CB, Comart C, Wegel C, Hall D, Hernandez D, Shiamim E, Riley E, Faghri F, Serrano GE, Chen H, Mata IF, Sarmiento IJK, Williamson J, Jankovic J, Shulman J, Solle JC, Murphy K, Nuytemans K, Kieburtz K, Markopoulou K, Marek K, Levine KS, Chahine LM, Ibanez L, Screven L, Ruffrage L, Shulman L, Marsili L, Kuhl M, Dean M, Koretsky M, Puckelwartz MJ, Inca-Martinez M, Louie N, Mencacci NE, Albin R, Alcalay R, Walker R, Chowdhury S, Dumanis S, Lubbe S, Xie T, Foroud T, Beach T, Sherer T, Song Y, Nguyen D, Nguyen T, Atadzhanov M, Blauwendraat C, Nalls MA, Foo JN, Mata I
Publication type: Article
Publication status: Published
Journal: Nature Genetics
Year: 2024
Volume: 56
Issue: 1
Pages: 27-36
Print publication date: 01/01/2024
Online publication date: 28/12/2023
Acceptance date: 20/10/2023
Date deposited: 30/01/2024
ISSN (print): 1061-4036
ISSN (electronic): 1546-1718
Publisher: Springer Nature
URL: https://doi.org/10.1038/s41588-023-01584-8
DOI: 10.1038/s41588-023-01584-8
Data Access Statement: GWAS summary statistics for Foo et al.2 and Loesch et al.3 are available upon request to the respective authors. The UKBB genotype and phenotype data are available through the UKBB web portal https://www.ukbiobank.ac.uk/. FinnGen summary statistics are available through the FinnGen website https://www.finngen.fi/. GWAS summary statistics for 23andMe datasets (post-Chang and data included in Chang et al.57 and Nalls et al.58) will be made available through 23andMe to qualified researchers under an agreement with 23andMe that protects the privacy of the 23andMe participants. Please visit research.23andme.com/collaborate/#publication for more information and to apply to access the data. An immediately accessible version of the multi-ancestry summary statistics is available on the Neurodegenerative Disease knowledge Portal (https://ndkp.hugeamp.org/) excluding Nalls et al.58, 23andMe post-Chang et al.57 and Web-Based Study of Parkinson’s Disease (PDWBS) but including all analyzed SNPs.
PubMed id: 38155330
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