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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 \u2018in-person\u2019 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.<\/jats:p>","DOI":"10.1101\/2025.01.31.25321395","type":"posted-content","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T19:15:12Z","timestamp":1738610112000},"source":"Crossref","is-referenced-by-count":3,"title":["Polygenic scores for disease risk are not associated with clinical outcomes in Parkinson\u2019s disease"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5835-669X","authenticated-orcid":false,"given":"Manuela MX","family":"Tan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotaka","family":"Iwaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Bandres-Ciga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri","family":"Sosero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Shoai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Brockmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigel M","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roy N","family":"Alcalay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jodi","family":"Maple-Gr\u00f8dem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Alves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ole-Bj\u00f8rn","family":"Tysnes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peggy","family":"Auinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirley","family":"Eberly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Heutink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David K.","family":"Simon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Kieburtz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Hardy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline H","family":"Williams-Gray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald G","family":"Grosset","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Christophe","family":"Corvol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziv","family":"Gan-Or","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Toft","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lasse","family":"Pihlstr\u00f8m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025020423450521000_2025.01.31.25321395v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(19)30320-5"},{"key":"2025020423450521000_2025.01.31.25321395v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-023-01584-8"},{"key":"2025020423450521000_2025.01.31.25321395v1.3","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-020-00763-0"},{"key":"2025020423450521000_2025.01.31.25321395v1.4","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27659"},{"key":"2025020423450521000_2025.01.31.25321395v1.5","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1002\/mds.26505","article-title":"A cumulative genetic risk score predicts motor progression in Parkinson\u2019s disease","volume":"31","year":"2016","journal-title":"Mov. 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