Dopamine pathway and Parkinson's risk variants are associated with levodopa-induced dyskinesia.

GBA1 LRRK2 Parkinson’s disease dopamine levodopa-induced dyskinesia

Journal

medRxiv : the preprint server for health sciences
Titre abrégé: medRxiv
Pays: United States
ID NLM: 101767986

Informations de publication

Date de publication:
20 Sep 2023
Historique:
pubmed: 4 10 2023
medline: 4 10 2023
entrez: 4 10 2023
Statut: epublish

Résumé

Levodopa-induced dyskinesia (LID) is a common adverse effect of levodopa, one of the main therapeutics used to treat the motor symptoms of Parkinson's disease (PD). Previous evidence suggests a connection between LID and a disruption of the dopaminergic system as well as genes implicated in PD, including To investigate the effects of genetic variants on risk and time to LID. We performed a genome-wide association study (GWAS) and analyses focused on We found that This study suggests that variants implicated in PD and in the dopaminergic transmission pathway play a role in the risk/time to develop LID. Further studies will be necessary to examine how these findings can inform clinical care.

Sections du résumé

Background UNASSIGNED
Levodopa-induced dyskinesia (LID) is a common adverse effect of levodopa, one of the main therapeutics used to treat the motor symptoms of Parkinson's disease (PD). Previous evidence suggests a connection between LID and a disruption of the dopaminergic system as well as genes implicated in PD, including
Objectives UNASSIGNED
To investigate the effects of genetic variants on risk and time to LID.
Methods UNASSIGNED
We performed a genome-wide association study (GWAS) and analyses focused on
Results UNASSIGNED
We found that
Conclusions UNASSIGNED
This study suggests that variants implicated in PD and in the dopaminergic transmission pathway play a role in the risk/time to develop LID. Further studies will be necessary to examine how these findings can inform clinical care.

Identifiants

DOI: 10.1101/2023.08.28.23294610 PMID: 37790572 PMC: PMC10543218
pubmed: 37790572
doi: 10.1101/2023.08.28.23294610
pmc: PMC10543218
pii:
doi:

Types de publication

Preprint

Langues

eng

Déclaration de conflit d'intérêts

ZGO has received consulting fees from Lysosomal Therapeutics Inc., Idorsia, Prevail Therapeutics, Denali, Ono Therapeutics, Neuron23, Handl Therapeutics, UBC, Bial Biotech Inc., Bial, Deerfield, Guidepoint, Lighthouse and VanquaBio. None of these companies were involved in any parts of preparing, drafting and publishing this study. ZKW is partially supported by the NIH/NIA and NIH/NINDS (1U19AG063911, FAIN: U19AG063911), Mayo Clinic Center for Regenerative Medicine, the gifts from the Donald G. and Jodi P. Heeringa Family, the Haworth Family Professorship in Neurodegenerative Diseases fund, and The Albertson Parkinson's Research Foundation. He serves as PI or Co-PI on Biohaven Pharmaceuticals, Inc. (BHV4157-206) and Vigil Neuroscience, Inc. (VGL101-01.002, VGL101-01.201, PET tracer development protocol, Cfthsf1r biomarker and repository project, and ultra-high field MRI in the diagnosis and management of CSF1R-related adult-onset leukoencephalopathy with axonal spheroids and pigmented glia) projects/grants. He serves as Co-PI of the Mayo Clinic APDA Center for Advanced Research and as an external advisory board member for the Vigil Neuroscience, Inc., and as a consultant on neurodegenerative medical research for Eli Lilli & Company.

Auteurs

Yuri L Sosero (YL)

Department of Human Genetics, McGill University, Montréal, QC, Canada.
The Neuro (Montreal Neurological Institute-Hospital), McGill University, Montréal, QC, Canada.

Sara Bandres-Ciga (S)

Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes on Health, Bethesda, MD, USA.

Bart Ferwerda (B)

Department of Clinical Epidemiology and Biostatistics, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.

Maria T P Tocino (MTP)

Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.

Dìaz R Belloso (DR)

Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.

Pilar Gómez-Garre (P)

Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.

Johann Faouzi (J)

Sorbonne Université, Paris Brain Institute - ICM, Inserm, CNRS, Assistance Publique Hôpitaux de Paris, Department of Neurology, Pitié-Salpêtrière Hospital, Paris, France.
CREST, ENSAI, Campus de Ker-Lann, 51 Rue Blaise Pascal - BP 37203 35172 Bruz Cedex, France.

Pille Taba (P)

Department of Neurology and Neurosurgery, Institute of Clinical Medicine, University of Tartu, Tartu 50406, Estonia.

Lukas Pavelka (L)

Transversal Translational Medicine, Luxembourg Institute of Health (LIH), Strassen, Luxembourg.
Centre Hospitalier de Luxembourg (CHL), Strassen, Luxembourg.

Tainà M Marques (TM)

Transversal Translational Medicine, Luxembourg Institute of Health (LIH), Strassen, Luxembourg.

Clarissa P C Gomes (CPC)

Translational Neuroscience, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg.

Alexey Kolodkin (A)

Transversal Translational Medicine, Luxembourg Institute of Health (LIH), Strassen, Luxembourg.

Patrick May (P)

Transversal Translational Medicine, Luxembourg Institute of Health (LIH), Strassen, Luxembourg.
Centre Hospitalier de Luxembourg (CHL), Strassen, Luxembourg.

Lukasz M Milanowski (LM)

Department of Neurology Faculty of Health Science, Medical University of Warsaw, Warsaw, Poland.
Department of Neurology, Mayo Clinic Florida, Jacksonville, Florida, USA.

Zbigniew K Wszolek (ZK)

Department of Neurology, Mayo Clinic Florida, Jacksonville, Florida, USA.

Ryan J Uitti (RJ)

Department of Neurology, Mayo Clinic Florida, Jacksonville, Florida, USA.

Peter Heutink (P)

German Center for Neurodegenerative Diseases (DZNE).

Jacobus J van Hilten (JJ)

Department of Neurology, Leiden University Medical Center, Leiden.

David K Simon (DK)

Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School.

Shirley Eberly (S)

Department of Biostatistics and Computational Biology at the University of Rochester School of Medicine and Dentistry.

Ignacio Alvarez (I)

Department of Neurology, Hospital Universitari Mutua de Terrassa, Barcelona, Spain.

Lynne Krohn (L)

Department of Human Genetics, McGill University, Montréal, QC, Canada.
The Neuro (Montreal Neurological Institute-Hospital), McGill University, Montréal, QC, Canada.

Eric Yu (E)

Department of Human Genetics, McGill University, Montréal, QC, Canada.
The Neuro (Montreal Neurological Institute-Hospital), McGill University, Montréal, QC, Canada.

Kathryn Freeman (K)

Department of Human Genetics, McGill University, Montréal, QC, Canada.
The Neuro (Montreal Neurological Institute-Hospital), McGill University, Montréal, QC, Canada.

Uladzislau Rudakou (U)

Department of Human Genetics, McGill University, Montréal, QC, Canada.
The Neuro (Montreal Neurological Institute-Hospital), McGill University, Montréal, QC, Canada.

Jennifer A Ruskey (JA)

The Neuro (Montreal Neurological Institute-Hospital), McGill University, Montréal, QC, Canada.
Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada.

Farnaz Asayesh (F)

The Neuro (Montreal Neurological Institute-Hospital), McGill University, Montréal, QC, Canada.
Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada.

Manuel Menéndez-Gonzàlez (M)

Facultad de Medicina y Ciencias de la Salud, Universidad de Oviedo, Calle Julián Clavería s/n, 33006 Oviedo, Spain.
Department of Neurology, Hospital Universitario Central de Asturias, Avenida Roma s/n, 33011 Oviedo, Spain.
Instituto de Investigación Sanitaria del Principado de Asturias, Avenida Roma s/n, 33011 Oviedo, Spain.

Pau Pastor (P)

Department of Neurology, Hospital Universitari Mutua de Terrassa, Barcelona, Spain.
Unit of Neurodegenerative Diseases, Department of Neurology, University Hospital Germans Trias i Pujol and The Germans Trias i Pujol Research Institute (IGTP) Badalona, Barcelona, Spain.

Owen A Ross (OA)

Department of Neurology, Mayo Clinic Florida, Jacksonville, Florida, USA.

Rejko Krüger (R)

Transversal Translational Medicine, Luxembourg Institute of Health (LIH), Strassen, Luxembourg.
Centre Hospitalier de Luxembourg (CHL), Strassen, Luxembourg.
Translational Neuroscience, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg.

Jean-Christophe Corvol (JC)

CREST, ENSAI, Campus de Ker-Lann, 51 Rue Blaise Pascal - BP 37203 35172 Bruz Cedex, France.

Sulev Koks (S)

Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Murdoch, Australia.
Perron Institute for Neurological and Translational Science, Nedlands, Australia.

Pablo Mir (P)

Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
Departamento de Medicina, Facultad de Medicina, Universidad de Sevilla, Sevilla, Spain.

Rob M A De Bie (RMA)

Department of Neurology and Clinical Neurophysiology, Amsterdam University Medical Centers, Amsterdam Neuroscience, University of Amsterdam, Amsterdam, The Netherlands.

Hirotaka Iwaki (H)

Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes on Health, Bethesda, MD, USA.
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Data Tecnica International, Washington, District of Columbia, USA.

Ziv Gan-Or (Z)

Department of Human Genetics, McGill University, Montréal, QC, Canada.
The Neuro (Montreal Neurological Institute-Hospital), McGill University, Montréal, QC, Canada.
Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada.

Classifications MeSH