TY  - JOUR
AU  - Sosero, Yuri L
AU  - Bandres-Ciga, Sara
AU  - Ferwerda, Bart
AU  - Tocino, Maria T P
AU  - Belloso, Dìaz R
AU  - Gómez-Garre, Pilar
AU  - Faouzi, Johann
AU  - Taba, Pille
AU  - Pavelka, Lukas
AU  - Marques, Tainà M
AU  - Gomes, Clarissa P C
AU  - Kolodkin, Alexey
AU  - May, Patrick
AU  - Milanowski, Lukasz M
AU  - Wszolek, Zbigniew K
AU  - Uitti, Ryan J
AU  - Heutink, Peter
AU  - van Hilten, Jacobus J
AU  - Simon, David K
AU  - Eberly, Shirley
AU  - Alvarez, Ignacio
AU  - Krohn, Lynne
AU  - Yu, Eric
AU  - Freeman, Kathryn
AU  - Rudakou, Uladzislau
AU  - Ruskey, Jennifer A
AU  - Asayesh, Farnaz
AU  - Menéndez-Gonzàlez, Manuel
AU  - Pastor, Pau
AU  - Ross, Owen A
AU  - Krüger, Rejko
AU  - Corvol, Jean-Christophe
AU  - Koks, Sulev
AU  - Mir, Pablo
AU  - De Bie, Rob M A
AU  - Iwaki, Hirotaka
AU  - Gan-Or, Ziv
TI  - Dopamine Pathway and Parkinson's Risk Variants Are Associated with Levodopa-Induced Dyskinesia.
JO  - Movement disorders
VL  - 39
IS  - 10
SN  - 0885-3185
CY  - New York, NY
PB  - Wiley
M1  - DZNE-2024-01240
SP  - 1773 - 1783
PY  - 2024
AB  - 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
KW  - Humans
KW  - Levodopa: adverse effects
KW  - Parkinson Disease: genetics
KW  - Parkinson Disease: drug therapy
KW  - Dyskinesia, Drug-Induced: genetics
KW  - Male
KW  - Female
KW  - Aged
KW  - Leucine-Rich Repeat Serine-Threonine Protein Kinase-2: genetics
KW  - Glucosylceramidase: genetics
KW  - Middle Aged
KW  - Genome-Wide Association Study
KW  - Dopamine: metabolism
KW  - Antiparkinson Agents: adverse effects
KW  - Genetic Predisposition to Disease: genetics
KW  - Polymorphism, Single Nucleotide: genetics
KW  - GBA1 (Other)
KW  - LRRK2 (Other)
KW  - Parkinson's disease (Other)
KW  - dopamine (Other)
KW  - levodopa‐induced dyskinesia (Other)
KW  - Levodopa (NLM Chemicals)
KW  - Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 (NLM Chemicals)
KW  - Glucosylceramidase (NLM Chemicals)
KW  - LRRK2 protein, human (NLM Chemicals)
KW  - Dopamine (NLM Chemicals)
KW  - GBA protein, human (NLM Chemicals)
KW  - Antiparkinson Agents (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC11490412
C6  - pmid:39132902
DO  - DOI:10.1002/mds.29960
UR  - https://pub.dzne.de/record/272822
ER  -