Insights into ancestral diversity in Parkinson’s disease risk: a comparative assessment of polygenic risk scores

Saffie-Awad, Paula, Grant, Spencer M., Makarious, Mary B., Elsayed, Inas, Sanyaolu, Arinola O., Crea, Peter Wild, Schumacher Schuh, Artur F., Levine, Kristin S., Vitale, Dan, Koretsky, Mathew J., Kim, Jeffrey, Peixoto Leal, Thiago, Periñán, María Teresa, Dey, Sumit, Noyce, Alastair J., Reyes-Palomares, Armando, Rodriguez-Losada, Noela, Foo, Jia Nee, Mohamed, Wael, Heilbron, Karl, Norcliffe-Kaufmann, Lucy, undefined, undefined, Aslibekyan, Stella, Auton, Adam, Babalola, Elizabeth, Bell, Robert K., Bielenberg, Jessica, Bryc, Katarzyna, Bullis, Emily, Cannon, Paul, Coker, Daniella, Partida, Gabriel Cuellar, Dhamija, Devika, Das, Sayantan, Elson, Sarah L., Eriksson, Nicholas, Filshtein, Teresa, Fitch, Alison, Fletez-Brant, Kipper, Fontanillas, Pierre, Freyman, Will, Granka, Julie M., Hernandez, Alejandro, Hicks, Barry, Hinds, David A., Jewett, Ethan M., Jiang, Yunxuan, Kukar, Katelyn, Kwong, Alan, Lin, Keng-Han, Llamas, Bianca A., Lowe, Maya, McCreight, Jey C., McIntyre, Matthew H., Micheletti, Steven J., Moreno, Meghan E., Nandakumar, Priyanka, Nguyen, Dominique T., Noblin, Elizabeth S., O’Connell, Jared, Petrakovitz, Aaron A., Poznik, G. David, Reynoso, Alexandra, Schloetter, Madeleine, Schumacher, Morgan, Shastri, Anjali J., Shelton, Janie F., Shi, Jingchunzi, Shringarpure, Suyash, Su, Qiaojuan Jane, Tat, Susana A., Tchakouté, Christophe Toukam, Tran, Vinh, Tung, Joyce Y., Wang, Xin, Wang, Wei, Weldon, Catherine H., Wilton, Peter, Wong, Corinna D., Rizig, Mie, Okubadejo, Njideka, Nalls, Mike A., Blauwendraat, Cornelis, Singleton, Andrew, Leonard, Hampton, undefined, undefined, Gatto, Emilia M., Kauffman, Marcelo, Khachatryan, Samson, Tavadyan, Zaruhi, Shepherd, Claire E., Hunter, Julie, Kumar, Kishore, Ellis, Melina, Rentería, Miguel E., Koks, Sulev, Zimprich, Alexander, Rieder, Carlos, Tumas, Vitor, Camargos, Sarah, Fon, Edward A., Monchi, Oury, Fon, Ted, Galleguillos, Benjamin Pizarro, Miranda, Marcelo, Bustamante, Maria Leonor, Olguin, Patricio, Chana, Pedro, Tang, Beisha, Shang, Huifang, Guo, Jifeng, Chan, Piu, Luo, Wei, Arboleda, Gonzalo, Orozco, Jorge, del Rio, Marlene Jimenez, Hernandez, Alvaro, Salama, Mohamed, Kamel, Walaa A., Zewde, Yared Z., Brice, Alexis, Corvol, Jean-Christophe, Westenberger, Ana, Illarionova, Anastasia, Mollenhauer, Brit, Klein, Christine, Vollstedt, Eva-Juliane, Hopfner, Franziska, Höglinger, Günter, Madoev, Harutyun, Trinh, Joanne, Junker, Johanna, Lohmann, Katja, Lange, Lara M., Sharma, Manu, Groppa, Sergio, Gasser, Thomas, Fang, Zih-Hua, Akpalu, Albert, Xiromerisiou, Georgia, Hadjigeorgiou, Georgios, Dagklis, Ioannis, Tarnanas, Ioannis, Stefanis, Leonidas, Stamelou, Maria, Dardiotis, Efthymios, Medina, Alex, Chan, Germaine Hiu-Fai, Ip, Nancy, Cheung, Nelson Yuk-Fai, Chan, Phillip, Zhou, Xiaopu, Kishore, Asha, Divya, K. P., Pal, Pramod, Kukkle, Prashanth Lingappa, Rajan, Roopa, Borgohain, Rupam, Salari, Mehri, Quattrone, Andrea, Valente, Enza Maria, Parnetti, Lucilla, Avenali, Micol, Schirinzi, Tommaso, Funayama, Manabu, Hattori, Nobutaka, Shiraishi, Tomotaka, Karimova, Altynay, Kaishibayeva, Gulnaz, Shambetova, Cholpon, Krüger, Rejko, Tan, Ai Huey, Ahmad-Annuar, Azlina, Norlinah, Mohamed Ibrahim, Murad, Nor Azian Abdul, Azmin, Shahrul, Lim, Shen-Yang, Tay, Yi Wen, Martinez-Ramirez, Daniel, Rodriguez-Violante, Mayela, Reyes-Pérez, Paula, Tserensodnom, Bayasgalan, Ojha, Rajeev, Anderson, Tim J., Pitcher, Toni L., Ojo, Oluwadamilola, Aasly, Jan O., Pihlstrøm, Lasse, Tan, Manuela, Ur-Rehman, Shoaib, Cornejo-Olivas, Mario, Doquenia, Maria Leila, Rosales, Raymond, Vinuela, Angel, Iakovenko, Elena, Mubarak, Bashayer Al, Umair, Muhammad, Tan, Eng-King, Amod, Ferzana, Carr, Jonathan, Bardien, Soraya, Jeon, Beomseok, Kim, Yun Joong, Cubo, Esther, Alvarez, Ignacio, Hoenicka, Janet, Beyer, Katrin, Pastor, Pau, El-Sadig, Sarah, Zweier, Christiane, Krack, Paul, Lin, Chin-Hsien, Wu, Hsiu-Chuan, Kung, Pin-Jui, Wu, Ruey-Meei, Wu, Serena, Wu, Yih-Ru, Amouri, Rim, Ben Sassi, Samia, Başak, A. Nazl, Genc, Gencer, Çakmak, Özgür Öztop, Ertan, Sibel, Martínez-Carrasco, Alejandro, Schrag, Anette, Schapira, Anthony, Carroll, Camille, Bale, Claire, Grosset, Donald, Stafford, Eleanor J., Houlden, Henry, Morris, Huw R., Hardy, John, Mok, Kin Y., Wood, Nicholas, Williams, Nigel ORCID: https://orcid.org/0000-0003-1177-6931, Okunoye, Olaitan, Lewis, Patrick A., Kaiyrzhanov, Rauan, Weil, Rimona, Love, Seth, Stott, Simon, Jasaitye, Simona, Obese, Vida, Espay, Alberto, O’Grady, Alyssa, Sobering, Andrew K., Siddiqi, Bernadette, Casey, Bradford, Fiske, Brian, Jonas, Cabell, Cruchaga, Carlos, Pantazis, Caroline B., Comart, Charisse, Wegel, Claire, Hall, Deborah, Hernandez, Dena, Shamim, Ejaz, Riley, Ekemini, Faghri, Faraz, Serrano, Geidy E., Iwaki, Hirotaka, Chen, Honglei, Sarmiento, Ignacio Juan Keller, Williamson, Jared, Jankovic, Joseph, Shulman, Joshua, Solle, Justin C., Murphy, Kaileigh, Nuytemans, Karen, Kieburtz, Karl, Markopoulou, Katerina, Marek, Kenneth, Chahine, Lana M., Screven, Laurel, Ruffrage, Lauren, Shulman, Lisa, Marsili, Luca, Kuhl, Maggie, Dean, Marissa, Inca-Martinez, Miguel, Louie, Naomi, Mencacci, Niccolò E., Albin, Roger, Alcalay, Roy, Walker, Ruth, Chowdhury, Sohini, Dumanis, Sonya, Lubbe, Steven, Xie, Tao, Foroud, Tatiana, Beach, Thomas, Sherer, Todd, Song, Yeajin, Nguyen, Duan, Nguyen, Toan, Atadzhanov, Masharip, Mata, Ignacio F. and Bandres-Ciga, Sara 2025. Insights into ancestral diversity in Parkinson’s disease risk: a comparative assessment of polygenic risk scores. npj Parkinson's Disease 11 , 201. 10.1038/s41531-025-00967-4

Full text not available from this repository.

Abstract

Risk prediction models play a crucial role in advancing healthcare by enabling early detection and supporting personalized medicine. Nonetheless, polygenic risk scores (PRS) for Parkinson’s disease (PD) have not been extensively studied across diverse populations, contributing to health disparities. In this study, we constructed 105 PRS using individual-level data from seven ancestries and compared two different models. Model 1 was based on the cumulative effect of 90 known European PD risk variants, weighted by summary statistics from four independent ancestries (European, East Asian, Latino/Admixed American, and African/Admixed). Model 2 leveraged multi-ancestry summary statistics using a p-value thresholding approach to improve prediction across diverse populations. Our findings provide a comprehensive assessment of PRS performance across ancestries and highlight the limitations of a “one-size-fits-all” approach to genetic risk prediction. We observed variability in predictive performance between models, underscoring the need for larger sample sizes and ancestry-specific approaches to enhance accuracy. These results establish a foundation for future research aimed at improving generalizability in genetic risk prediction for PD.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine
Publisher:	Springer Science and Business Media LLC
Date of Acceptance:	14 April 2025
Last Modified:	18 Aug 2025 13:48
URI:	https://orca.cardiff.ac.uk/id/eprint/180508

Actions (repository staff only)

Edit Item