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

Kim, Jonggeol Jeffrey and Vitale, Dan and Otani, Diego Veliz and Lian, Michelle Mulan and Heilbron, Karl and Aslibekyan, Stella and Auton, Adam and Babalola, Elizabeth and Bell, Robert K. and Bielenberg, Jessica and Bryc, Katarzyna and Bullis, Emily and Cannon, Paul and Coker, Daniella and Partida, Gabriel Cuellar and Dhamija, Devika and Das, Sayantan and Elson, Sarah L. and Eriksson, Nicholas and Filshtein, Teresa and Fitch, Alison and Fletez-Brant, Kipper and Fontanillas, Pierre and Freyman, Will and Granka, Julie M. and Hernandez, Alejandro and Hicks, Barry and Hinds, David A. and Jewett, Ethan M. and Jiang, Yunxuan and Kukar, Katelyn and Kwong, Alan and Lin, Keng-Han and Llamas, Bianca A. and Lowe, Maya and McCreight, Jey C. and McIntyre, Matthew H. and Micheletti, Steven J. and Moreno, Meghan E. and Nandakumar, Priyanka and Nguyen, Dominique T. and Noblin, Elizabeth S. and O'Connell, Jared and Petrakovitz, Aaron A. and Poznik, G. David and Reynoso, Alexandra and Schloetter, Madeleine and Schumacher, Morgan and Shastri, Anjali J. and Shelton, Janie F. and Shi, Jingchunzi and Shringarpure, Suyash and Su, Qiaojuan Jane and Tat, Susana A. and Tchakoute, Christophe Toukam and Tran, Vinh and Tung, Joyce Y. and Wang, Xin and Wang, Wei and Weldon, Catherine H. and Wilton, Peter and Wong, Corinna D. and Iwaki, Hirotaka and Lake, Julie and Solsberg, Caroline Warly and Leonard, Hampton and Makarious, Mary B. and Tan, Eng-King and Singleton, Andrew B. and Bandres-Ciga, Sara and Noyce, Alastair J. and Gatto, Emilia M. and Kauffman, Marcelo and Khachatryan, Samson and Tavadyan, Zaruhi and Shepherd, Claire E. and Hunter, Julie and Kumar, Kishore and Ellis, Melina and Renteria, Miguel E. and Koks, Sulev and Zimprich, Alexander and Schumacher-Schuh, Artur F. and Rieder, Carlos and Awad, Paula Saffie and Tumas, Vitor and Camargos, Sarah and Fon, Edward A. and Monchi, Oury and Fon, Ted and Galleguillos, Benjamin Pizarro and Miranda, Marcelo and Bustamante, Maria Leonor and Olguin, Patricio and Chana, Pedro and Tang, Beisha and Shang, Huifang and Guo, Jifeng and Chan, Piu and Luo, Wei and Arboleda, Gonzalo and Orozc, Jorge and del Rio, Marlene Jimenez and Hernandez, Alvaro and Salama, Mohamed and Kamel, Walaa A. and Zewde, Yared Z. and Brice, Alexis and Corvol, Jean-Christophe and Westenberger, Ana and Illarionova, Anastasia and Mollenhauer, Brit and Klein, Christine and Vollstedt, Eva-Juliane and Hopfner, Franziska and Hoglinger, Gunter and Madoev, Harutyun and Trinh, Joanne and Junker, Johanna and Lohmann, Katja and Lange, Lara M. and Sharma, Manu and Groppa, Sergiu and Gasser, Thomas and Fang, Zih-Hua and Akpalu, Albert and Xiromerisiou, Georgia and Hadjigorgiou, Georgios and Dagklis, Ioannis and Tarnanas, Ioannis and Stefanis, Leonidas and Stamelou, Maria and Dadiotis, Efthymios and Medina, Alex and Chan, Germaine Hiu-Fai and Ip, Nancy and Cheung, Nelson Yuk-Fai and Chan, Phillip and Zhou, Xiaopu and Kishore, Asha and Divya, K. P. and Pal, Pramod and Kukkle, Prashanth Lingappa and Rajan, Roopa and Borgohain, Rupam and Salari, Mehri and Quattrone, Andrea and Valente, Enza Maria and Parnetti, Lucilla and Avenali, Micol and Schirinzi, Tommaso and Funayama, Manabu and Hattori, Nobutaka and Shiraishi, Tomotaka and Karimova, Altynay and Kaishibayeva, Gulnaz and Shambetova, Cholpon and Krueger, Rejko and Tan, Ai Huey and Ahmad-Annuar, Azlina and Norlinah, Mohamed Ibrahim and Murad, Nor Azian Abdul and Azmin, Shahrul and Lim, Shen-Yang and Mohamed, Wael and Tay, Yi Wen and Martinez-Ramirez, Daniel and Rodriguez-Violante, Mayela and Reyes-Perez, Paula and Tserensodnom, Bayasgalan and Ojha, Rajeev and Anderson, Tim J. and Pitcher, Toni L. and Sanyaolu, Arinola and Okubadejo, Njideka and Ojo, Oluwadamilola and Aasly, Jan O. and Pihlstrom, Lasse and Tan, Manuela and Ur-Rehman, Shoaib and Veliz-Otani, Diego and Cornejo-Olivas, Mario and Doquenia, Maria Leila and Rosales, Raymond and Vinuela, Angel and Iakovenko, Elena and Al Mubarak, Bashayer and Umair, Muhammad and Amod, Ferzana and Carr, Jonathan and Bardien, Soraya and Jeon, Beomseok and Kim, Yun Joong and Cubo, Esther and Alvarez, Ignacio and Hoenicka, Janet and Beyer, Katrin and Perinan, Maria Teresa and Pastor, Pau and El-Sadig, Sarah and Brolin, Kajsa and Zweier, Christiane and Tinkhauser, Gerd and Krack, Paul and Lin, Chin-Hsien and Wu, Hsiu-Chuan and Kung, Pin-Jui and Wu, Ruey-Meei and Wu, Yihru and Amouri, Rim and Ben Sassi, Samia and Basak, A. Nazl and Genc, Gencer and Cakmak, Ozguer Oztop and Ertan, Sibel and Martinez-Carrasco, Alejandro and Schrag, Anette and Schapira, Anthony and Carroll, Camille and Bale, Claire and Grosset, Donald and Stafford, Eleanor J. and Houlden, Henry and Morris, Huw R. and Hardy, John and Mok, Kin Ying and Rizig, Mie and Wood, Nicholas and Williams, Nigel and Okunoye, Olaitan and Lewis, Patrick Alfryn and Kaiyrzhanov, Rauan and Weil, Rimona and Love, Seth and Stott, Simon and Jasaityte, Simona and Dey, Sumit and Obese, Vida and Espay, Alberto and O'Grady, Alyssa and Sobering, Andrew K. and Siddiqi, Bernadette and Casey, Bradford and Fiske, Brian and Jonas, Cabell and Cruchaga, Carlos and Pantazis, Caroline B. and Comart, Charisse and Wegel, Claire and Hall, Deborah and Hernandez, Dena and Shiamim, Ejaz and Riley, Ekemini and Faghri, Faraz and Serrano, Geidy E. and Chen, Honglei and Mata, Ignacio F. and Sarmiento, Ignacio Juan Keller and Williamson, Jared and Jankovic, Joseph and Shulman, Joshua and Solle, Justin C. and Murphy, Kaileigh and Nuytemans, Karen and Kieburtz, Karl and Markopoulou, Katerina and Marek, Kenneth and Levine, Kristin S. and Chahine, Lana M. and Ibanez, Laura and Screven, Laurel and Ruffrage, Lauren and Shulman, Lisa and Marsili, Luca and Kuhl, Maggie and Dean, Marissa and Koretsky, Mathew and Puckelwartz, Megan J. and Inca-Martinez, Miguel and Louie, Naomi and Mencacci, Niccolo Emanuele and Albin, Roger and Alcalay, Roy and Walker, Ruth and Chowdhury, Sohini and Dumanis, Sonya and Lubbe, Steven and Xie, Tao and Foroud, Tatiana and Beach, Thomas and Sherer, Todd and Song, Yeajin and Nguyen, Duan and Nguyen, Toan and Atadzhanov, Masharip and Blauwendraat, Cornelis and Nalls, Mike A. and Foo, Jia Nee and Mata, Ignacio and Team, 23andMe Res and Program, Global Parkinson Genetics (2024) Multi-ancestry genome-wide association meta-analysis of Parkinson's disease. Nature Genetics, 56 (1). ISSN 1061-4036, DOI https://doi.org/10.1038/s41588-023-01584-8.

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Official URL: https://doi.org/10.1038/s41588-023-01584-8

Abstract

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. Multi-ancestry genome-wide association analyses identify new risk loci for Parkinson's disease, and fine-mapping and co-localization analyses implicate candidate genes whose expression is associated with disease susceptibility.

Item Type: Article
Funders: UNSPECIFIED
Uncontrolled Keywords: Genome; Parkinson; disease
Subjects: R Medicine > R Medicine (General)
Divisions: Universiti Malaya
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 14 Nov 2024 04:57
Last Modified: 14 Nov 2024 04:57
URI: http://eprints.um.edu.my/id/eprint/45923

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