Genetic Stratification of Age-Dependent Parkinson's Disease Risk by Polygenic Hazard Score.

Autor:	Pihlstrøm L; Department of Neurology, Oslo University Hospital, Oslo, Norway., Fan CC; Department of Cognitive Science, University of California San Diego, La Jolla, California, USA.; Center for Multimodal Imaging and Genetics, School of Medicine, University of California San Diego, La Jolla, California, USA., Frei O; NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Center for Bioinformatics, Department of Informatics, University of Oslo, Oslo, Norway., Tan M; Department of Neurology, Oslo University Hospital, Oslo, Norway., Karunamuni RA; Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California, USA., Blauwendraat C; Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA., Bandres-Ciga S; Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA., Gan-Or Z; Montreal Neurological Institute, McGill University, Montreal, Québec, Canada.; Department of Human Genetics, McGill University, Montreal, Québec, Canada.; Department of Neurology and Neurosurgery, McGill University, Montreal, Québec, Canada., Grosset DG; Department of Neurology, Queen Elizabeth University Hospital, Glasgow, United Kingdom., Dale AM; Department of Cognitive Science, University of California San Diego, La Jolla, California, USA.; Center for Multimodal Imaging and Genetics, School of Medicine, University of California San Diego, La Jolla, California, USA.; NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Radiology, University of California San Diego, La Jolla, California, USA.; Department of Neurosciences, University of California San Diego, La Jolla, California, USA., Seibert TM; Center for Multimodal Imaging and Genetics, School of Medicine, University of California San Diego, La Jolla, California, USA.; NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California, USA.; Department of Radiology, University of California San Diego, La Jolla, California, USA.; Department of Bioengineering, University of California San Diego, La Jolla, California, USA., Andreassen OA; NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Jazyk:	angličtina
Zdroj:	Movement disorders : official journal of the Movement Disorder Society [Mov Disord] 2022 Jan; Vol. 37 (1), pp. 62-69. Date of Electronic Publication: 2021 Oct 06.
DOI:	10.1002/mds.28808
Abstrakt:	Background: Parkinson's disease (PD) is a highly age-related disorder, where common genetic risk variants affect both disease risk and age at onset. A statistical approach that integrates these effects across all common variants may be clinically useful for individual risk stratification. A polygenic hazard score methodology, leveraging a time-to-event framework, has recently been successfully applied in other age-related disorders. Objectives: We aimed to develop and validate a polygenic hazard score model in sporadic PD. Methods: Using a Cox regression framework, we modeled the polygenic hazard score in a training data set of 11,693 PD patients and 9841 controls. The score was then validated in an independent test data set of 5112 PD patients and 5372 controls and a small single-study sample of 360 patients and 160 controls. Results: A polygenic hazard score predicts the onset of PD with a hazard ratio of 3.78 (95% confidence interval 3.49-4.10) when comparing the highest to the lowest risk decile. Combined with epidemiological data on incidence rate, we apply the score to estimate genetically stratified instantaneous PD risk across age groups. Conclusions: We demonstrate the feasibility of a polygenic hazard approach in PD, integrating the genetic effects on disease risk and age at onset in a single model. In combination with other predictive biomarkers, the approach may hold promise for risk stratification in future clinical trials of disease-modifying therapies, which aim at postponing the onset of PD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. (© 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)
Databáze:	MEDLINE
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