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Record W4412008894 · doi:10.1038/s41531-025-00967-4

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

2025· article· en· W4412008894 on OpenAlexaff
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, 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, 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, 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, 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, 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

Bibliographic record

Venuenpj Parkinson s Disease · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsMcGill University
FundersNational Institute of Neurological Disorders and StrokeNational Institute on AgingU.S. Department of Health and Human ServicesNational Institutes of HealthArizona Department of Health ServicesMichael J. Fox Foundation for Parkinson's Research
KeywordsGeneralizability theoryPolygenic risk scoreDiseaseRisk assessmentMedicineBiologyPsychologyComputer scienceGeneticsInternal medicineGeneDevelopmental psychology

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.011
metaresearch head score (Gemma)0.029
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.011
Threshold uncertainty score0.059

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0110.029
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.002
Bibliometrics0.0020.002
Science and technology studies0.0010.001
Scholarly communication0.0020.001
Open science0.0000.002
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.022
GPT teacher head0.318
Teacher spread0.296 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations5
Published2025
Admission routes1
Has abstractyes

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