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@ARTICLE{Sosero:272822,
author = {Sosero, Yuri L and Bandres-Ciga, Sara and Ferwerda, Bart
and Tocino, Maria T P and Belloso, Dìaz R and Gómez-Garre,
Pilar and Faouzi, Johann and Taba, Pille and Pavelka, Lukas
and Marques, Tainà M and Gomes, Clarissa P C and Kolodkin,
Alexey and May, Patrick and Milanowski, Lukasz M and
Wszolek, Zbigniew K and Uitti, Ryan J and Heutink, Peter and
van Hilten, Jacobus J and Simon, David K and Eberly, Shirley
and Alvarez, Ignacio and Krohn, Lynne and Yu, Eric and
Freeman, Kathryn and Rudakou, Uladzislau and Ruskey,
Jennifer A and Asayesh, Farnaz and Menéndez-Gonzàlez,
Manuel and Pastor, Pau and Ross, Owen A and Krüger, Rejko
and Corvol, Jean-Christophe and Koks, Sulev and Mir, Pablo
and De Bie, Rob M A and Iwaki, Hirotaka and Gan-Or, Ziv},
collaboration = {Consortium, NCER-PD and Consortium, International
Parkinson's Disease Genomic},
othercontributors = {Acharya, Geeta and Aguayo, Gloria and Alexandre, Myriam and
Ali, Muhammad and Ammerlann, Wim and Arena, Giuseppe and
Balling, Rudi and Bassis, Michele and Beaumont, Katy and
Becker, Regina and Bellora, Camille and Berchem, Guy and
Berg, Daniela and Bisdorff, Alexandre and Boussaad, Ibrahim
and Brockmann, Kathrin and Calme, Jessica and Castillo,
Lorieza and Contesotto, Gessica and Diederich, Nico and
Dondelinger, Rene and Esteves, Daniela and Fagherazzi, Guy
and Ferrand, Jean-Yves and Gantenbein, Manon and Gasser,
Thomas and Gawron, Piotr and Ghosh, Soumyabrata and
Giraitis, Marijus and Glaab, Enrico and De Lope, Elisa
Gómez and Graas, Jérôme and Graziano, Mariella and
Groues, Valentin and Grünewald, Anne and Gu, Wei and
Hammot, Gaël and Hanff, Anne-Marie and Hansen, Linda and
Heneka, Michael and Henr, Estelle and Herbrink, Sylvia and
Herzinger, Sascha and Heymann, Michael and Hu, Michele and
Hundt, Alexander and Jacoby, Nadine and Lebioda, Jacek
Jaroslaw and Jaroz, Yohan and Jónsdóttir, Sonja and
Klopfenstein, Quentin and Klucken, Jochen and Krüger, Rejko
and Lambert, Pauline and Landoulsi, Zied and Lentz, Roseline
and Liepelt-Scarfone, Inga and Liszka, Robert and Longhino,
Laura and Lorentz, Victoria and Lupu, Paula Cristina and
Marques, Tainá M and Mackay, Clare and Maetzler, Walter and
Marcus, Katrin and Marques, Guilherme and Conde, Patricia
Martins and May, Patrick and Mcintyre, Deborah and Mediouni,
Chouaib and Meisch, Francoise and Menster, Myriam and
Minelli, Maura and Mittelbronn, Michel and Mollenhauer, Brit
and Mühlschlegel, Friedrich and Nati, Romain and Nehrbass,
Ulf and Nickels, Sarah and Nicolai, Beatrice and Nicolay,
Jean-Paul and Noor, Fozia and Ostaszewski, Marek and Gomes,
Clarissa P C and Pachchek, Sinthuja and Pauly, Claire and
Pauly, Laure and Pavelka, Lukas and Perquin, Magali and
Lima, Rosalina Ramos and Rauschenberger, Armin and Rawal,
Rajesh and Bobbili, Dheeraj Reddy and Roomp, Kirsten and
Rosales, Eduardo and Rosety, Isabel and Sandt, Estelle and
Sapienza, Stefano and Satagopam, Venkata and Schmitt,
Margaux and Schmitz, Sabine and Schneide, Reinhard and
Schwamborn, Jens and Sharify, Amir and Soboleva, Ekaterina
and Sokolowska, Kate and Thien, Hermann and Thiry, Elodie
and Loo, Rebecca Ting Jiin and Trefois, Christophe and
Trouet, Johanna and Tsurkalenko, Olena and Vaillant, Michel
and Valenti, Mesele and Van Cutsem, Gilles and Vega, Carlos
and Boas, Liliana Vilas and Vyas, Maharshi and Wade-Martins,
Richard and Wilmes, Paul and Wollscheid-Lengeling, Evi and
Zelimkhanov, Gelani},
title = {{D}opamine {P}athway and {P}arkinson's {R}isk {V}ariants
{A}re {A}ssociated with {L}evodopa-{I}nduced {D}yskinesia.},
journal = {Movement disorders},
volume = {39},
number = {10},
issn = {0885-3185},
address = {New York, NY},
publisher = {Wiley},
reportid = {DZNE-2024-01240},
pages = {1773 - 1783},
year = {2024},
abstract = {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.Our goal was 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 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.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 $(ORfourth_quartile$
= 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 $(HRthird_quartile$ =
1.38; $95\%$ CI, 1.07-1.79; P = 0.0128; $HRfourth_quartile$
= 1.38; $95\%$ CI = 1.06-1.78; P = 0.0147).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.},
keywords = {Humans / Levodopa: adverse effects / Parkinson Disease:
genetics / Parkinson Disease: drug therapy / Dyskinesia,
Drug-Induced: genetics / Male / Female / Aged / Leucine-Rich
Repeat Serine-Threonine Protein Kinase-2: genetics /
Glucosylceramidase: genetics / Middle Aged / Genome-Wide
Association Study / Dopamine: metabolism / Antiparkinson
Agents: adverse effects / Genetic Predisposition to Disease:
genetics / Polymorphism, Single Nucleotide: genetics / GBA1
(Other) / LRRK2 (Other) / Parkinson's disease (Other) /
dopamine (Other) / levodopa‐induced dyskinesia (Other) /
Levodopa (NLM Chemicals) / Leucine-Rich Repeat
Serine-Threonine Protein Kinase-2 (NLM Chemicals) /
Glucosylceramidase (NLM Chemicals) / LRRK2 protein, human
(NLM Chemicals) / Dopamine (NLM Chemicals) / GBA protein,
human (NLM Chemicals) / Antiparkinson Agents (NLM
Chemicals)},
cin = {AG Heutink},
ddc = {610},
cid = {I:(DE-2719)1210002},
pnm = {354 - Disease Prevention and Healthy Aging (POF4-354)},
pid = {G:(DE-HGF)POF4-354},
typ = {PUB:(DE-HGF)16},
pmc = {pmc:PMC11490412},
pubmed = {pmid:39132902},
doi = {10.1002/mds.29960},
url = {https://pub.dzne.de/record/272822},
}