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

作者：Paula Saffie Awad, Spencer Grant, Mary B. Makarious, Inas Elsayed, Arinola O. Sanyaolu, Peter Wild Crea, Artur Francisco Schumacher Schuh, Kristin Levine, Dan Vitale, Mathew J. Koretsky, Jeffrey Kim, Thiago Peixoto Leal, María Teresa Periñán, Sumit Dey, Alastair J. Noyce, Armando Reyes‐Palomares, Noela Rodríguez-Losada, Jia Nee Foo, Wael Mohamed, Karl Heilbron, Lucy Norcliffe‐Kaufmann, Stella Aslibekyan, Adam Auton, Elizabeth Babalola, Robert K. Bell, Jessica Bielenberg, Katarzyna Bryc, Emily Bullis, P. F. Cannon, Daniella Coker, Gabriel Cuéllar-Partida, Devika Dhamija, Sayantan Das, Sarah L. Elson, Nicholas Eriksson, Teresa Filshtein, Alison Fitch, Kipper Fletez‐Brant, Pierre Fontanillas, Will Freyman, Julie M. Granka, Alejandro Hernandez, Barry Hicks, David A. Hinds, Ethan M. Jewett, Yunxuan Jiang, Katelyn Kukar, Alan Kwong, Keng‐Han Lin, Bianca A. Llamas, Maya Lowe, Jey C. McCreight, Matthew H. McIntyre, Steven J. Micheletti, Meghan E. Moreno, Priyanka Nandakumar, Dominique T. Nguyen, Elizabeth S. Noblin, Jared O’Connell, Aaron A. Petrakovitz, G. David Poznik, Alexandra Reynoso, Madeleine Schloetter, Morgan Schumacher, Anjali J. Shastri, Janie F. Shelton, Jingchunzi Shi, Suyash Shringarpure, Qiaojuan Jane Su, Susana A. Tat, Christophe Toukam Tchakouté, Vinh Tran, Joyce Y. Tung, Xin Wang, Wei Wang, Catherine H. Weldon, Peter Wilton, Corinna D. Wong, Mie Rizig, Njideka Okubadejo, Mike A. Nalls, Cornelis Blauwendraat, Andrew B. Singleton, Hampton L. Leonard, Global Parkinson’s Genetics Program (GP2), Emilia Gatto, Marcelo Kauffman, Samson Khachatryan, Zaruhi Tavadyan, Claire E. Shepherd, Julie Hunter, Kishore R. Kumar, Melina Ellis, Miguel E. Rentería, Sulev Kõks, Alexander Zimprich, Carlos Roberto de Mello Rieder, Vítor Tumas, Sarah Camargos, Edward A. Fon, Oury Monchi, Ted Fon, Benjamin Pizarro Galleguillos, Marcelo Miranda, M. Leonor Bustamante, Patricio Olguı́n, Pedro Chaná, Beisha Tang, Huifang Shang, Jifeng Guo, Piu Chan, Wei Luo, Gonzálo Arboleda, Jorge Orozco, Marlene Jiménez-Del-Río, Alvaro Hernandez, Mohamed Salama, Walaa A. Kamel, Yared Z. Zewde, Alexis Brice, Jean‐Christophe Corvol, Ana Westenberger, Anastasia Illarionova, Brit Mollenhauer, Christine Klein, Eva‐Juliane Vollstedt, Franziska Hopfner, Günter U. Höglinger, Harutyun Madoev, Joanne Trinh, Johanna Junker, Katja Lohmann, Lara M. Lange, Manu Sharma, Sergiu Groppa, Thomas Gasser, Zih‐Hua Fang, Albert Akpalu, Georgia Xiromerisiou, Georgios M. Hadjigeorgiou, Ioannis Dagklis, Ioannis Tarnanas, Leonidas Stefanis, María Stamelou, Efthimios Dardiotis, Alex Medina, Germaine Hiu-Fai Chan, Nancy Y. Ip, Nelson Yuk-Fai Cheung, Phillip Chan, Xiaopu Zhou, Asha Kishore, K. P. Divya, Pramod Pal, Prashanth Lingappa Kukkle, Roopa Rajan, Rupam Borgohain, Mehri Salari, Andrea Quattrone, Enza Maria Valente, Lucilla Parnetti, Micol Avenali, Tommaso Schirinzi, Manabu Funayama, Nobutaka Hattori, Tomotaka Shiraishi, Altynay Karimova, Gulnaz Kaishibayeva, Cholpon Shambetova, Rejko Krüger, Ai Huey Tan, Azlina Ahmad‐Annuar, Mohamed Ibrahim Norlinah, Nor Azian Abdul Murad, Shahrul Azmin, Shen‐Yang Lim, Yi Wen Tay, Daniel Martínez-Ramírez, Mayela Rodríguez‐Violante, Paula Reyes‐Pérez, Bayasgalan Tserensodnom, Rajeev Ojha, Tim Anderson, Toni L. Pitcher, Oluwadamilola O. Ojo, Jan Aasly, Lasse Pihlstrøm, Manuela Tan, Shoaib Ur-Rehman, Mario Cornejo‐Olivas, Maria Leila M. Doquenia, Raymond L. Rosales, Ángel Viñuela, Е. А. Яковенко, Bashayer Al Mubarak, Muhammad Umair, Eng-King Tan, Ferzana Amod, Jonathan Carr, Soraya Bardien, Beomseok Jeon, Yun Joong Kim, Esther Cubo, Ignacio Álvarez, Janet Hoenicka, Katrin Beyer, Pau Pástor, Sarah El-Sadig, Christiane Zweier, Paul Krack, Chin‐Hsien Lin, Hsiu-Chuan Wu, Pin‐Jui Kung, Ruey‐Meei Wu, Serena Wu, Yih‐Ru Wu, Rim Amouri, Samia Ben Sassi, A. Nazl Başak, Gençer Genç, Özgür Öztop Çakmak, Sibel Ertan, Alejandro Martínez-Carrasco, Anette Schrag, Anthony H.V. Schapira, Camille Carroll, Claire Bale, Donald G. Grosset, Eleanor J. Stafford, Henry Houlden, Huw R. Morris, John Hardy, Kin Y. Mok, Nicholas Wood, Nigel Williams, Olaitan Okunoye, Patrick A. Lewis, Rauan Kaiyrzhanov, Rimona S. Weil, Seth Love, Simon Stott, Simona Jasaitye, Vida Obese, Alberto J. Espay, Alyssa O’Grady, Andrew K. Sobering, Bernadette Siddiqi, Bradford Casey, Brian Fiske, Cabell Jonas, Carlos Cruchaga, Caroline B. Pantazis, Charisse Comart, Claire Wegel, Deborah A. Hall, Dena Hernandez, Ejaz A. Shamim, Ekemini Riley, Faraz Faghri, Geidy E. Serrano, Hirotaka Iwaki, Honglei Chen, Ignacio Juan Keller Sarmiento, Jared Williamson, Joseph Jankovic, Joshua Shulman, J Solle, Kaileigh Murphy, Karen Nuytemans, Karl Kieburtz, Katerina Markopoulou, Kenneth Marek, Lana M. Chahine, Laurel A. Screven, Lauren Ruffrage, Lisa Shulman, Luca Marsili, Maggie Kuhl, Marissa Dean, Miguel Inca‐Martinez, Naomi Louie, Niccolò E. Mencacci, Roger L. Albin, Roy N. Alcalay, Ruth Walker, Sohini Chowdhury, Sonya B. Dumanis, Steven Lubbe, Tao Xie, Tatiana M. Foroud, Thomas G. Beach, Todd Sherer, Yeajin Song, Duan Nguyen, Toan Nguyen, Masharip Atadzhanov, Ignácio F. Mata, Sara Bandrés‐Ciga · 发表于：npj Parkinson s Disease · 年份：2025 · DOI：10.1038/s41531-025-00967-4 · 被引用次数：5 · 研究领域：Genetic Associations and Epidemiology、Genomic variations and chromosomal abnormalities、RNA regulation and disease

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.