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Multi-ancestry genome-wide association meta-analysis of Parkinson’s disease

Lookup NU author(s): Professor Camille CarrollORCiD

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Abstract

© 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.

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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

PubMed id: 38155330

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