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

Paula Saffie-Awad; Spencer M Grant; Mary B Makarious; Inas Elsayed; Arinola O Sanyaolu; Peter Wild Crea; Artur F Schumacher Schuh; Kristin S Levine; Dan Vitale; Mathew J Koretsky; Jeffrey Kim; Thiago Peixoto Leal; María Teresa Periñán; Sumit Dey; Alastair J Noyce; Armando Reyes-Palomares; Noela Rodriguez-Losada; Jia Nee Foo; Wael Mohamed; Karl Heilbron; Lucy Norcliffe-Kaufmann; null null; Stella Aslibekyan; Adam Auton; Elizabeth Babalola; Robert K Bell; Jessica Bielenberg; Katarzyna Bryc; Emily Bullis; Paul Cannon; Daniella Coker; Gabriel Cuellar 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 Singleton; Hampton Leonard; Emilia M Gatto; Marcelo Kauffman; Samson Khachatryan; Zaruhi Tavadyan; Claire E Shepherd; Julie Hunter; Kishore Kumar; Melina Ellis; Miguel E Rentería; Sulev Koks; Alexander Zimprich; Carlos Rieder; Vitor Tumas; Sarah Camargos; Edward A Fon; Oury Monchi; Ted Fon; Benjamin Pizarro Galleguillos; Marcelo Miranda; Maria Leonor Bustamante; Patricio Olguin; Pedro Chana; Beisha Tang; Huifang Shang; Jifeng Guo; Piu Chan; Wei Luo; Gonzalo Arboleda; Jorge Orozco; Marlene Jimenez del Rio; 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 Höglinger; Harutyun Madoev; Joanne Trinh; Johanna Junker; Katja Lohmann; Lara M Lange; Manu Sharma; Sergio Groppa; Thomas Gasser; Zih-Hua Fang; Albert Akpalu; Georgia Xiromerisiou; Georgios Hadjigeorgiou; Ioannis Dagklis; Ioannis Tarnanas; Leonidas Stefanis; Maria Stamelou; Efthymios Dardiotis; Alex Medina; Germaine Hiu-Fai Chan; Nancy 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 Martinez-Ramirez; Mayela Rodriguez-Violante; Paula Reyes-Pérez; Bayasgalan Tserensodnom; Rajeev Ojha; Tim J Anderson; Toni L Pitcher; Oluwadamilola Ojo; Jan O Aasly; Lasse Pihlstrøm; Manuela Tan; Shoaib Ur-Rehman; Mario Cornejo-Olivas; Maria Leila Doquenia; Raymond Rosales; Angel Vinuela; Elena Iakovenko; Bashayer Al Mubarak; Muhammad Umair; Eng-King Tan; Ferzana Amod; Jonathan Carr; Soraya Bardien; Beomseok Jeon; Yun Joong Kim; Esther Cubo; Ignacio Alvarez; Janet Hoenicka; Katrin Beyer; Pau Pastor; 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; Gencer Genc; Özgür Öztop Çakmak; Sibel Ertan; Alejandro Martínez-Carrasco; Anette Schrag; Anthony Schapira; Camille Carroll; Claire Bale; Donald 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 Weil; Seth Love; Simon Stott; Simona Jasaitye; Vida Obese; Alberto 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 Hall; Dena Hernandez; Ejaz Shamim; Ekemini Riley; Faraz Faghri; Geidy E Serrano; Hirotaka Iwaki; Honglei Chen; Ignacio Juan Keller Sarmiento; Jared Williamson; Joseph Jankovic; Joshua Shulman; Justin C Solle; Kaileigh Murphy; Karen Nuytemans; Karl Kieburtz; Katerina Markopoulou; Kenneth Marek; Lana M Chahine; Laurel Screven; Lauren Ruffrage; Lisa Shulman; Luca Marsili; Maggie Kuhl; Marissa Dean; Miguel Inca-Martinez; Naomi Louie; Niccolò E Mencacci; Roger Albin; Roy Alcalay; Ruth Walker; Sohini Chowdhury; Sonya Dumanis; Steven Lubbe; Tao Xie; Tatiana Foroud; Thomas Beach; Todd Sherer; Yeajin Song; Duan Nguyen; Toan Nguyen; Masharip Atadzhanov; Ignacio F Mata; Sara Bandres-Ciga

doi:10.1038/s41531-025-00967-4

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

Journal article

Open access

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

Paula Saffie-Awad, Spencer M Grant, Mary B Makarious, Inas Elsayed, Arinola O Sanyaolu, Peter Wild Crea, Artur F Schumacher Schuh, Kristin S Levine, Dan Vitale, Mathew J Koretsky, …

NPJ PARKINSON'S DISEASE, Vol.11(1), 201

2025

DOI: https://doi.org/10.1038/s41531-025-00967-4

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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.

Details

Title: Insights into ancestral diversity in Parkinson’s disease risk: a comparative assessment of polygenic risk scores
Authors/Creators: Paula Saffie-Awad
Spencer M Grant - Institute on Aging
Mary B Makarious - National Institute on Aging
Inas Elsayed - University of Gezira
Arinola O Sanyaolu - University of Lagos
Peter Wild Crea - Institute on Aging
Artur F Schumacher Schuh
Kristin S Levine - Data Tecnica International (United States)
Dan Vitale - Data Tecnica International (United States)
Mathew J Koretsky - National Institutes of Health
Jeffrey Kim - Institute on Aging
Thiago Peixoto Leal
María Teresa Periñán - Biomedical Research Networking Center on Neurodegenerative Diseases
Sumit Dey - Queen Mary University of London
Alastair J Noyce - Queen Mary University of London
Armando Reyes-Palomares - Universidad de Málaga
Noela Rodriguez-Losada - Universidad de Málaga
Jia Nee Foo - Nanyang Technological University
Wael Mohamed - Menoufia University
Karl Heilbron - 23andMe (United States)
Lucy Norcliffe-Kaufmann - 23andMe (United States)
null null
Stella Aslibekyan
Adam Auton
Elizabeth Babalola
Robert K Bell
Jessica Bielenberg
Katarzyna Bryc
Emily Bullis
Paul Cannon
Daniella Coker
Gabriel Cuellar 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 - University College London
Njideka Okubadejo - University of Lagos
Mike A Nalls - Data Tecnica International (United States)
Cornelis Blauwendraat - Institute on Aging
Andrew Singleton - Institute on Aging
Hampton Leonard - Data Tecnica International (United States)
Emilia M Gatto
Marcelo Kauffman
Samson Khachatryan
Zaruhi Tavadyan
Claire E Shepherd
Julie Hunter
Kishore Kumar
Melina Ellis
Miguel E Rentería
Sulev Koks
Alexander Zimprich
Carlos Rieder
Vitor Tumas
Sarah Camargos
Edward A Fon
Oury Monchi
Ted Fon
Benjamin Pizarro Galleguillos
Marcelo Miranda
Maria Leonor Bustamante
Patricio Olguin
Pedro Chana
Beisha Tang
Huifang Shang
Jifeng Guo
Piu Chan
Wei Luo
Gonzalo Arboleda
Jorge Orozco
Marlene Jimenez del Rio
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 Höglinger
Harutyun Madoev
Joanne Trinh
Johanna Junker
Katja Lohmann
Lara M Lange
Manu Sharma
Sergio Groppa
Thomas Gasser
Zih-Hua Fang
Albert Akpalu
Georgia Xiromerisiou
Georgios Hadjigeorgiou
Ioannis Dagklis
Ioannis Tarnanas
Leonidas Stefanis
Maria Stamelou
Efthymios Dardiotis
Alex Medina
Germaine Hiu-Fai Chan
Nancy 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 Martinez-Ramirez
Mayela Rodriguez-Violante
Paula Reyes-Pérez
Bayasgalan Tserensodnom
Rajeev Ojha
Tim J Anderson
Toni L Pitcher
Oluwadamilola Ojo
Jan O Aasly
Lasse Pihlstrøm
Manuela Tan
Shoaib Ur-Rehman
Mario Cornejo-Olivas
Maria Leila Doquenia
Raymond Rosales
Angel Vinuela
Elena Iakovenko
Bashayer Al Mubarak
Muhammad Umair
Eng-King Tan
Ferzana Amod
Jonathan Carr
Soraya Bardien
Beomseok Jeon
Yun Joong Kim
Esther Cubo
Ignacio Alvarez
Janet Hoenicka
Katrin Beyer
Pau Pastor
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
Gencer Genc
Özgür Öztop Çakmak
Sibel Ertan
Alejandro Martínez-Carrasco
Anette Schrag
Anthony Schapira
Camille Carroll
Claire Bale
Donald 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 Weil
Seth Love
Simon Stott
Simona Jasaitye
Vida Obese
Alberto 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 Hall
Dena Hernandez
Ejaz Shamim
Ekemini Riley
Faraz Faghri
Geidy E Serrano
Hirotaka Iwaki
Honglei Chen
Ignacio Juan Keller Sarmiento
Jared Williamson
Joseph Jankovic
Joshua Shulman
Justin C Solle
Kaileigh Murphy
Karen Nuytemans
Karl Kieburtz
Katerina Markopoulou
Kenneth Marek
Lana M Chahine
Laurel Screven
Lauren Ruffrage
Lisa Shulman
Luca Marsili
Maggie Kuhl
Marissa Dean
Miguel Inca-Martinez
Naomi Louie
Niccolò E Mencacci
Roger Albin
Roy Alcalay
Ruth Walker
Sohini Chowdhury
Sonya Dumanis
Steven Lubbe
Tao Xie
Tatiana Foroud
Thomas Beach
Todd Sherer
Yeajin Song
Duan Nguyen
Toan Nguyen
Masharip Atadzhanov
Ignacio F Mata - Cleveland Clinic
Sara Bandres-Ciga - National Institute on Aging
Publication Details: NPJ PARKINSON'S DISEASE, Vol.11(1), 201
Publisher: Springer Nature
Number of pages: 13
Identifiers: 991005828144307891
Copyright: © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2025
Murdoch Affiliation: Personalised Medicine Centre
Language: English
Resource Type: Journal article

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Collaboration types: Industry collaboration; Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.189 Genome Studies; 1.189.455 Genome-Wide Association Studies
Web Of Science research areas: Neurosciences
ESI research areas: Neuroscience & Behavior