DOAJ Open Access 2025

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 +26 lainnya

Abstrak

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.

Topik & Kata Kunci

Neurology. Diseases of the nervous system

Penulis (31)

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

the 23andMe Research Team

Mie Rizig

Njideka Okubadejo

Mike A. Nalls

Cornelis Blauwendraat

Andrew Singleton

Hampton Leonard

Global Parkinson’s Genetics Program (GP2)

Ignacio F. Mata

Sara Bandres-Ciga

Format Sitasi

APA MLA BibTeX

Saffie-Awad, P., Grant, S.M., Makarious, M.B., Elsayed, I., Sanyaolu, A.O., Crea, P.W. et al. (2025). Insights into ancestral diversity in Parkinson’s disease risk: a comparative assessment of polygenic risk scores. https://doi.org/10.1038/s41531-025-00967-4

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Informasi Jurnal

Tahun Terbit: 2025
Sumber Database: DOAJ
DOI: 10.1038/s41531-025-00967-4
Akses: Open Access ✓