medRxiv : the preprint server for health sciences · 2025
Polygenic scores for disease risk are not associated with clinical outcomes in Parkinson's disease.
СтатьяПрепринтНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Tan Manuela Mx, Iwaki Hirotaka, Bandres-Ciga Sara, Sosero Yuri, Shoai Maryam, Brockmann Kathrin, Williams Nigel M, Alcalay Roy N, Maple-Grødem Jodi, Alves Guido, Tysnes Ole-Bjørn, Auinger Peggy, Eberly Shirley, Heutink Peter, Simon David K, Kieburtz Karl, Hardy John, Williams-Gray Caroline H, Grosset Donald G, Corvol Jean-Christophe, Gan-Or Ziv, Toft Mathias, Pihlstrøm Lasse
Аннотация
Polygenic risk scores (PRS) in Parkinson's disease (PD) are associated with disease risk. Recently, pathway-specific PRS have been created to take advantage of annotations inking variants to biological pathways or cell types. Here, we investigated 8 biological pathways or regions of open chromatin using pathway-specific PRS: alpha-synuclein pathway, adaptive immunity, innate immunity, lysosomal pathway1, endocytic membrane-trafficking pathway, mitochondrial pathway, microglial open chromatin single nucleotide polymorphisms (SNPs), and monocyte open chromatin SNPs. We analysed 7,402 PD patients across 18 'in-person' PD cohorts, and 6,717 patients from the online Fox Insight study. We did not find any significant associations between the 8 pathway-specific PRSs and 8 clinical outcomes in PD. Though this may be due to a lack of statistical power and limited sample size, it may also suggest that the genetic architecture of sporadic PD risk is different from the genetics of PD progression and clinical outcomes.