Polygenic Parkinson's Disease Genetic Risk Score as Risk Modifier of Parkinsonism in Gaucher Disease

Cornelis Blauwendraat; Nahid Tayebi; Elizabeth Geena Woo; Grisel Lopez; Luca Fierro; Marco Toffoli; Naomi Limbachiya; Derralynn Hughes; Vanessa Pitz; Dhairya Patel; Dan Vitale; Mathew J. Koretsky; Dena Hernandez; Raquel Real; Roy N. Alcalay; Mike A. Nalls; Huw R. Morris; Anthony H.V. Schapira; Manisha Balwani; Ellen Sidransky

doi:10.1002/mds.29342

Polygenic Parkinson's Disease Genetic Risk Score as Risk Modifier of Parkinsonism in Gaucher Disease

Cornelis Blauwendraat^*, Nahid Tayebi, Elizabeth Geena Woo, Grisel Lopez, Luca Fierro, Marco Toffoli, Naomi Limbachiya, Derralynn Hughes, Vanessa Pitz, Dhairya Patel, Dan Vitale, Mathew J. Koretsky, Dena Hernandez, Raquel Real, Roy N. Alcalay, Mike A. Nalls, Huw R. Morris, Anthony H.V. Schapira, Manisha Balwani, Ellen Sidransky^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

Background: Biallelic pathogenic variants in GBA1 are the cause of Gaucher disease (GD) type 1 (GD1), a lysosomal storage disorder resulting from deficient glucocerebrosidase. Heterozygous GBA1 variants are also a common genetic risk factor for Parkinson's disease (PD). GD manifests with considerable clinical heterogeneity and is also associated with an increased risk for PD. Objective: The objective of this study was to investigate the contribution of PD risk variants to risk for PD in patients with GD1. Methods: We studied 225 patients with GD1, including 199 without PD and 26 with PD. All cases were genotyped, and the genetic data were imputed using common pipelines. Results: On average, patients with GD1 with PD have a significantly higher PD genetic risk score than those without PD (P = 0.021). Conclusions: Our results indicate that variants included in the PD genetic risk score were more frequent in patients with GD1 who developed PD, suggesting that common risk variants may affect underlying biological pathways.

Original language	English
Pages (from-to)	899-903
Number of pages	5
Journal	Movement Disorders
Volume	38
Issue number	5
DOIs	https://doi.org/10.1002/mds.29342
State	Published - May 2023
Externally published	Yes

Funding

Funders	Funder number
Center for Alzheimer's and Related Dementias
National Institutes of Health and Cure Parkinson's (UK)
National Institutes of Health
U.S. Department of Health and Human Services
National Institute on Aging
National Human Genome Research Institute
National Institute of Neurological Disorders and Stroke

Keywords

GBA1
Gaucher
Parkinson's
genetics

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10.1002/mds.29342

Cite this

Blauwendraat, C., Tayebi, N., Woo, E. G., Lopez, G., Fierro, L., Toffoli, M., Limbachiya, N., Hughes, D., Pitz, V., Patel, D., Vitale, D., Koretsky, M. J., Hernandez, D., Real, R., Alcalay, R. N., Nalls, M. A., Morris, H. R., Schapira, A. H. V., Balwani, M., & Sidransky, E. (2023). Polygenic Parkinson's Disease Genetic Risk Score as Risk Modifier of Parkinsonism in Gaucher Disease. Movement Disorders, 38(5), 899-903. https://doi.org/10.1002/mds.29342

@article{1204f41724794fc9811d2b4afffe9c00,

title = "Polygenic Parkinson's Disease Genetic Risk Score as Risk Modifier of Parkinsonism in Gaucher Disease",

abstract = "Background: Biallelic pathogenic variants in GBA1 are the cause of Gaucher disease (GD) type 1 (GD1), a lysosomal storage disorder resulting from deficient glucocerebrosidase. Heterozygous GBA1 variants are also a common genetic risk factor for Parkinson's disease (PD). GD manifests with considerable clinical heterogeneity and is also associated with an increased risk for PD. Objective: The objective of this study was to investigate the contribution of PD risk variants to risk for PD in patients with GD1. Methods: We studied 225 patients with GD1, including 199 without PD and 26 with PD. All cases were genotyped, and the genetic data were imputed using common pipelines. Results: On average, patients with GD1 with PD have a significantly higher PD genetic risk score than those without PD (P = 0.021). Conclusions: Our results indicate that variants included in the PD genetic risk score were more frequent in patients with GD1 who developed PD, suggesting that common risk variants may affect underlying biological pathways.",

keywords = "GBA1, Gaucher, Parkinson's, genetics",

author = "Cornelis Blauwendraat and Nahid Tayebi and Woo, {Elizabeth Geena} and Grisel Lopez and Luca Fierro and Marco Toffoli and Naomi Limbachiya and Derralynn Hughes and Vanessa Pitz and Dhairya Patel and Dan Vitale and Koretsky, {Mathew J.} and Dena Hernandez and Raquel Real and Alcalay, {Roy N.} and Nalls, {Mike A.} and Morris, {Huw R.} and Schapira, {Anthony H.V.} and Manisha Balwani and Ellen Sidransky",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.",

year = "2023",

month = may,

doi = "10.1002/mds.29342",

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Blauwendraat, C, Tayebi, N, Woo, EG, Lopez, G, Fierro, L, Toffoli, M, Limbachiya, N, Hughes, D, Pitz, V, Patel, D, Vitale, D, Koretsky, MJ, Hernandez, D, Real, R, Alcalay, RN, Nalls, MA, Morris, HR, Schapira, AHV, Balwani, M & Sidransky, E 2023, 'Polygenic Parkinson's Disease Genetic Risk Score as Risk Modifier of Parkinsonism in Gaucher Disease', Movement Disorders, vol. 38, no. 5, pp. 899-903. https://doi.org/10.1002/mds.29342

TY - JOUR

T1 - Polygenic Parkinson's Disease Genetic Risk Score as Risk Modifier of Parkinsonism in Gaucher Disease

AU - Blauwendraat, Cornelis

AU - Tayebi, Nahid

AU - Woo, Elizabeth Geena

AU - Lopez, Grisel

AU - Fierro, Luca

AU - Toffoli, Marco

AU - Limbachiya, Naomi

AU - Hughes, Derralynn

AU - Pitz, Vanessa

AU - Patel, Dhairya

AU - Vitale, Dan

AU - Koretsky, Mathew J.

AU - Hernandez, Dena

AU - Real, Raquel

AU - Alcalay, Roy N.

AU - Nalls, Mike A.

AU - Morris, Huw R.

AU - Schapira, Anthony H.V.

AU - Balwani, Manisha

AU - Sidransky, Ellen

N1 - Publisher Copyright: © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

PY - 2023/5

Y1 - 2023/5

N2 - Background: Biallelic pathogenic variants in GBA1 are the cause of Gaucher disease (GD) type 1 (GD1), a lysosomal storage disorder resulting from deficient glucocerebrosidase. Heterozygous GBA1 variants are also a common genetic risk factor for Parkinson's disease (PD). GD manifests with considerable clinical heterogeneity and is also associated with an increased risk for PD. Objective: The objective of this study was to investigate the contribution of PD risk variants to risk for PD in patients with GD1. Methods: We studied 225 patients with GD1, including 199 without PD and 26 with PD. All cases were genotyped, and the genetic data were imputed using common pipelines. Results: On average, patients with GD1 with PD have a significantly higher PD genetic risk score than those without PD (P = 0.021). Conclusions: Our results indicate that variants included in the PD genetic risk score were more frequent in patients with GD1 who developed PD, suggesting that common risk variants may affect underlying biological pathways.

AB - Background: Biallelic pathogenic variants in GBA1 are the cause of Gaucher disease (GD) type 1 (GD1), a lysosomal storage disorder resulting from deficient glucocerebrosidase. Heterozygous GBA1 variants are also a common genetic risk factor for Parkinson's disease (PD). GD manifests with considerable clinical heterogeneity and is also associated with an increased risk for PD. Objective: The objective of this study was to investigate the contribution of PD risk variants to risk for PD in patients with GD1. Methods: We studied 225 patients with GD1, including 199 without PD and 26 with PD. All cases were genotyped, and the genetic data were imputed using common pipelines. Results: On average, patients with GD1 with PD have a significantly higher PD genetic risk score than those without PD (P = 0.021). Conclusions: Our results indicate that variants included in the PD genetic risk score were more frequent in patients with GD1 who developed PD, suggesting that common risk variants may affect underlying biological pathways.

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JF - Movement Disorders

IS - 5

ER -

Polygenic Parkinson's Disease Genetic Risk Score as Risk Modifier of Parkinsonism in Gaucher Disease

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