TY - JOUR
T1 - Genetic stratification of motor and QoL outcomes in Parkinson's disease in the EARLYSTIM study
AU - Weiss, Daniel
AU - Landoulsi, Zied
AU - May, Patrick
AU - Sharma, Manu
AU - Schüpbach, Michael
AU - You, Hana
AU - Corvol, Jean Christophe
AU - Paschen, Steffen
AU - Helmers, Ann Kristin
AU - Barbe, Michael
AU - Fink, Gereon
AU - Kühn, Andrea A.
AU - Courbon, Christine Brefel
AU - Wojtecki, Lars
AU - Damier, Philippe
AU - Fraix, Valerie
AU - Houeto, Jean Luc
AU - Regis, Jean
AU - Sixel-Döring, Friederike
AU - Pinsker, Marcus O.
AU - Thobois, Stephane
AU - Gharabaghi, Alireza
AU - Stoker, Valerie
AU - Timmermann, Lars
AU - Schnitzler, Alfons
AU - Krack, Paul
AU - Vidailhet, Marie
AU - Deuschl, Günther
AU - Krüger, Rejko
N1 - Funding Information:
We would like thank the EarlyStim Investigators for contributing blood specimens and clinical data to this genetic study. Moreover, we would like to thank Medtronic, Minneapolis, Minnesota, USA for financial support of this ancillary study for consumables and processing. A substantial institutional support provided as in-kind contributions of data storage capacity, data curation capacity, data analyses (statisticians, bioinformaticians) and genotyping/processing of sequencing Chips (technical assistants, consumables) was provided by the Center for Neurology, Hertie-Institute for Clinical Brain Research, University of Tübingen (Germany) and the Luxembourg Center for Systems Biomedicine (LCSB), University of Luxembourg (Luxembourg).
Publisher Copyright:
© 2022 Elsevier Ltd
PY - 2022/10
Y1 - 2022/10
N2 - Purpose: The decision for subthalamic deep brain stimulation (STN-DBS) in Parkinson's disease (PD) relies on clinical predictors. Whether genetic variables could predict favourable or unfavourable decisions is under investigation. Objective: First, we aimed to reproduce the previous observation that SNCA rs356220 was associated with favourable STN-DBS motor response. In additional exploratory analyses, we studied if other PD risk and progression variants from the latest GWAS are associated with therapeutic outcome. Further, we evaluated the predictive value of polygenic risk scores. Methods: We comprehensively genotyped patients from the EarlyStim cohort using NeuroChip, and assessed the clinico-genetic associations with longitudinal outcome parameters. Results: The SNCA rs356220 variant did not predict UPDRS III outcomes. However, it was associated with quality of life improvement in secondary analyses. Several polymorphisms from previously identified GWAS hits predicted motor or quality of life outcomes in DBS patients. Polygenic risk scores did not predict any outcome parameter. Conclusions: Our findings support the hypothesis that different common genetic markers are associated with favourable quality of life outcomes of STN-DBS in PD. These findings can be the basis for further validation in larger and independent cohorts.
AB - Purpose: The decision for subthalamic deep brain stimulation (STN-DBS) in Parkinson's disease (PD) relies on clinical predictors. Whether genetic variables could predict favourable or unfavourable decisions is under investigation. Objective: First, we aimed to reproduce the previous observation that SNCA rs356220 was associated with favourable STN-DBS motor response. In additional exploratory analyses, we studied if other PD risk and progression variants from the latest GWAS are associated with therapeutic outcome. Further, we evaluated the predictive value of polygenic risk scores. Methods: We comprehensively genotyped patients from the EarlyStim cohort using NeuroChip, and assessed the clinico-genetic associations with longitudinal outcome parameters. Results: The SNCA rs356220 variant did not predict UPDRS III outcomes. However, it was associated with quality of life improvement in secondary analyses. Several polymorphisms from previously identified GWAS hits predicted motor or quality of life outcomes in DBS patients. Polygenic risk scores did not predict any outcome parameter. Conclusions: Our findings support the hypothesis that different common genetic markers are associated with favourable quality of life outcomes of STN-DBS in PD. These findings can be the basis for further validation in larger and independent cohorts.
KW - Alpha-synuclein
KW - Deep brain stimulation
KW - Genetic association
KW - Parkinson's disease
UR - http://www.scopus.com/inward/record.url?scp=85138155569&partnerID=8YFLogxK
UR - https://pubmed.ncbi.nlm.nih.gov/36117018
U2 - 10.1016/j.parkreldis.2022.08.025
DO - 10.1016/j.parkreldis.2022.08.025
M3 - Article
C2 - 36117018
SN - 1353-8020
VL - 103
SP - 169
EP - 174
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
ER -