Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Pihlstrom L

PROVIDER: S-EPMC9843635 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Publications

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

Pihlstrøm Lasse L Fan Chun C CC Frei Oleksandr O Tan Manuela M Karunamuni Roshan A RA Blauwendraat Cornelis C Bandres-Ciga Sara S Gan-Or Ziv Z Grosset Donald G DG Dale Anders M AM Seibert Tyler M TM Andreassen Ole A OA

Movement disorders : official journal of the Movement Disorder Society 20211006 1

<h4>Background</h4>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.<h4>Objectives</h4>We aimed to develop and validate a pol ...[more]

PMID: 34612543

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Dataset Information

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

Background

Objectives

Methods

Results

Conclusions

Publications

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

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