Dopamine Pathway and Parkinson's Risk Variants Are Associated with Levodopa-Induced Dyskinesia
Sosero, Y.L. (McGill University)
Bandres-Ciga, Sara (Department of Health and Human Services. Center for Alzheimer's and Related Dementias (CARD). National Institute on Aging and National Institute of Neurological Disorders and Stroke. National Institutes on Health)
Ferwerda, Bart (Universiteit van Amsterdam)
Tocino, Maria T.P. (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Belloso, Diaz R. (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Gómez-Garre, Pilar (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Faouzi, Johann (Sorbonne Université)
Taba, Pille (University of Tartu)
Pavelka, Lukas (Luxembourg Institute of Health (LIH))
Marques, Tainà M. (Luxembourg Institute of Health (LIH))
Gomes, Clarissa P.C. (University of Luxembourg)
Kolodkin, Alexey (Luxembourg Institute of Health (LIH))
May, Patrick (Luxembourg Institute of Health (LIH))
Milanowski, Lukasz (Mayo Clinic Florida (Jacksonville, Estats Units d'Amèrica))
Wszolek, Zbigniew K. (Mayo Clinic Florida (Jacksonville, Estats Units d'Amèrica))
Uitti, Ryan J. (Mayo Clinic Florida (Jacksonville, Estats Units d'Amèrica))
Heutink, Peter (German Center for Neurodegenerative Diseases (DZNE))
van Hilten, Jacobus J. (Leiden University Medical Center)
Simon, David K. (Beth Israel Deaconess Cancer Center (Boston, Estats Units d'Amèrica))
Eberly, Shirley (University of Rochester School of Medicine and Dentistry)
Alvarez, Ignacio (Hospital Universitari MútuaTerrassa (Terrassa, Catalunya))
Krohn, Lynne (McGill University)
Yu, Eric (McGill University)
Freeman, Kathryn (McGill University)
Rudakou, Uladzislau (McGill University)
Ruskey, Jennifer A. (McGill University)
Asayesh, Farnaz (McGill University)
Mendez-Gonzalez, Manuel (Hospital Universitario Central de Asturias)
Pastor, Pau (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Ross, Owen A. (Mayo Clinic Florida (Jacksonville, Estats Units d'Amèrica))
Krüger, Rejko (University of Luxembourg)
Corvol, Jean-Christophe (CREST-ENSAI (Rennes, França). Department of Economics and Statistics)
Koks, Sulev (Neurological and Translational Science. Perron Institute)
Mir, Pablo (Universidad de Sevilla)
De Bie, Rob M.A. (Universiteit van Amsterdam)
Iwaki, Hirotaka (National Institute on Aging and National Institute of Neurological Disorders and Stroke)
Gan-Or, Ziv (McGill University)
Acharya, Geeta (Luxembourg Institute of Health)
Aguayo, Gloria (Luxembourg Institute of Health)
Alexandre, Myriam (Luxembourg Institute of Health)
Ali, Muhammad (University of Luxembourg)
Ammerlann, Wim (Luxembourg Institute of Health)
Arena, Giuseppe (University of Luxembourg)
Balling, Rudi (University of Luxembourg)
Bassis, Michele (University of Luxembourg)
Beaumont, Katy (Luxembourg Institute of Health)
Becker, Regina (University of Luxembourg)
Bellora, Camille (Luxembourg Institute of Health)
Berchem, Guy (Centre Hospitalier de Luxembourg)
Berg, Daniela (University Hospital of Tübingen (Alemanya))
Bisdorff, Alexandre (Centre Hospitalier Emile Mayrisch)
Boussaad, Ibrahim (University of Luxembourg)
Brockmann, Kathrin (University Hospital of Tübingen (Alemanya))
Calme, Jessica (Luxembourg Institute of Health)
Castillo, Lorieza (Luxembourg Institute of Health)
Contesotto, Gessica (Luxembourg Institute of Health)
Diederich, Nico (Centre Hospitalier de Luxembourg)
Dondelinger, Rene (Centre Hospitalier Emile Mayrisch)
Esteves, Daniela (Luxembourg Institute of Health)
Fagherazzi, Guy (Luxembourg Institute of Health)
Ferrand, Jean-Yves (Luxembourg Institute of Health)
Gantenbein, Manon (Luxembourg Institute of Health)
Gasser, Thomas (University Hospital of Tübingen (Alemanya))
Gawron, Piotr (University of Luxembourg)
Ghosh, Soumyabrata (University of Luxembourg)
Giraitis, Marijus (Luxembourg Institute of Health)
Glaab, Enrico (University of Luxembourg)
Gómez De Lope, Elisa (University of Luxembourg)
Graas, Jérôme (Luxembourg Institute of Health)
Graziano, Mariella (Association of Physiotherapists in Parkinson's Disease Europe)
Groues, Valentin (University of Luxembourg)
Grünewald, Anne (University of Luxembourg)
Gu, Wei (University of Luxembourg)
Hammot, Gaël (Luxembourg Institute of Health)
Hanff, Anne-Marie (Luxembourg Institute of Health)
Hansen, Linda (University of Luxembourg)
Heneka, Michahel (University of Luxembourg)
Henr, Estelle (Luxembourg Institute of Health)
Herbrink, Sylvia (Centre Hospitalier du Nord)
Herzinger, Sascha (University of Luxembourg)
Heymann, Michael (Luxembourg Institute of Health)
Hu, Michele (University of Oxford)
Hundt, Alexander (Luxembourg Institute of Health)
Jacoby, Nadine (Private practice, Ettelbruck, Luxembourg)
Lebioda, Jacek Jaroslaw (University of Luxembourg)
Jaroz, Yohan (University of Luxembourg)
Jónsdóttir, Sonja (Luxembourg Institute of Health)
Klopfenstein, Quentin (University of Luxembourg)
Klucken, Jochen (University of Luxembourg)
Lambert, Pauline (Luxembourg Institute of Health)
Landoulsi, Zied (University of Luxembourg)
Lentz, Roseline (Parkinson Luxembourg Association)
Liepelt, Inga (University Hospital of Tübingen (Alemanya))
Liszka, Robert (Westpfalz-Klinikum GmbH, Kaiserslautern)
Longhino, Laura (Centre Hospitalier de Luxembourg)
Lorentz, Victoria (Luxembourg Institute of Health)
Lupu, Paula Cristina (Luxembourg Institute of Health)
Mackay, Clare (University of Oxford)
Maetzler, Walter (University Medical Center SchleswigHolstein)
Marcus, Katrin (Ruhr-Universität Bochum)
Marques, Guilherme (Luxembourg Institute of Health)
Conde, Patricia Martins (University of Luxembourg)
Mcintyre, Deborah (Luxembourg Institute of Health)
Mediouni, Chouaib (Luxembourg Institute of Health)
Meisch, Francoise (University of Luxembourg)
Menster, Myriam (Luxembourg Institute of Health)
Minelli, Maura (Luxembourg Institute of Health)
Mittelbronn, Michel (University of Luxembourg)
Mollenhauer, Brit (Paracelsus-Elena-Klinik, Kassel)
Mühlschlegel, Friedrich (Laboratoire National de Santé)
Nati, Romain (Centre Hospitalier de Luxembourg)
Nehrbass, Ulf (Luxembourg Institute of Health)
Nickels, Sarah (University of Luxembourg)
Nicolai, Beatrice (Centre Hospitalier de Luxembourg)
Nicolay, Jean-Pau (Private practice, Luxembourg)
Noor, Fozia (Luxembourg Institute of Health)
Ostaszewski, Marek (University of Luxembourg)
Pachchek, Sinthuja (University of Luxembourg)
Pauly, Claire (University of Luxembourg)
Pauly, Laure (University of Luxembourg)
Perquin, Magali (Luxembourg Institute of Health)
Lima, Rosalina Ramos (Luxembourg Institute of Health)
Rauschenberger, Armin (University of Luxembourg)
Rawal, Rajesh (University of Luxembourg)
Reddy Bobbili, Dheeraj (University of Luxembourg)
Roomp, Kirsten (University of Luxembourg)
Rosales, Eduardo 1836-1873 (Luxembourg Institute of Health)
Rosety, Isabel (University of Luxembourg)
Sandt, Estelle (Luxembourg Institute of Health)
Sapienza, Stefano (University of Luxembourg)
Satagopam, Venkata (University of Luxembourg)
Schmitt, Margaux (Luxembourg Institute of Health)
Schmitz, Sabine (University of Luxembourg)
Schneide, Reinhard (University of Luxembourg)
Schwamborn, Jens (University of Luxembourg)
Sharify, Amir (Luxembourg Institute of Health)
Soboleva, Ekaterina (University of Luxembourg)
Sokolowska, Kate (Luxembourg Institute of Health)
Thien, Hermann (Luxembourg Institute of Health)
Thiry, Elodie (Centre Hospitalier de Luxembourg)
Loo, Rebecca Ting Jiin (University of Luxembourg)
Trefois, Christophe (University of Luxembourg)
Trouet, Johanna (Luxembourg Institute of Health)
Tsurkalenko, Olena (Luxembourg Institute of Health)
Vaillant, Michel (Luxembourg Institute of Health)
Valenti, Mesele (Luxembourg Institute of Health)
Van Cutsem, Gilles (University of Luxembourg)
Vega, Carlos (University of Luxembourg)
Boas, Liliana Vilas (Centre Hospitalier de Luxembourg)
Vyas, Maharshi (University of Luxembourg)
Wade-Martins, Richard (University of Oxford)
Wilmes, Paul (University of Luxembourg)
Wollscheid-Lengeling, Evi (University of Luxembourg)
Zelimkhanov, Gelani (Centre Hospitalier de Luxembourg)

Data:	2024
Resum:	Background: 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 GBA1 and LRRK2. Objectives: Our goal was to investigate the effects of genetic variants on risk and time to LID. Methods: We performed a genome-wide association study (GWAS) and analyses focused on GBA1 and LRRK2 variants. We also calculated polygenic risk scores (PRS) including risk variants for PD and variants in genes involved in the dopaminergic transmission pathway. To test the influence of genetics on LID risk we used logistic regression, and to examine its impact on time to LID we performed Cox regression including 1612 PD patients with and 3175 without LID. Results: We found that GBA1 variants were associated with LID risk (odds ratio [OR] = 1. 65; 95% confidence interval [CI], 1. 21-2. 26; P = 0. 0017) and LRRK2 variants with reduced time to LID onset (hazard ratio [HR] = 1. 42; 95% CI, 1. 09-1. 84; P = 0. 0098). The fourth quartile of the PD PRS was associated with increased LID risk (OR = 1. 27; 95% CI, 1. 03-1. 56; P = 0. 0210). The third and fourth dopamine pathway PRS quartiles were associated with a reduced time to development of LID (HR = 1. 38; 95% CI, 1. 07-1. 79; P = 0. 0128; HR = 1. 38; 95% CI = 1. 06-1. 78; P = 0. 0147). Conclusions: 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. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Levodopa-induced dyskinesia ; Parkinson's disease ; Dopamine ; GBA1 ; LRRK2
Publicat a:	Movement Disorders, Vol. 39 Núm. 10 (October 2024) , p. 1773-1783, ISSN 1531-8257

DOI: 10.1002/mds.29960
PMID: 39132902

11 p, 1.0 MB

El registre apareix a les col·leccions:
Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Articles de recerca
Articles > Articles publicats