Parkinson's disease; Deep brain stimulation; Alpha-synuclein; Genetic association
Résumé :
[en] 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.
Centre de recherche :
- Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) - Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group)
Disciplines :
Génétique & processus génétiques Neurologie
Auteur, co-auteur :
Weiss, Daniel
LANDOULSI, Zied ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core
MAY, Patrick ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core
Sharma, Manu
Schüpbach, Michael
You, Hana
Corvol, Jean Christophe
Paschen, Steffen
Helmers, Ann-Kristin
Barbe, Michael
Fink, Gereon
Kühn, Andrea A.
Courbon, Christine Brefel
Wojtecki, Lars
Damier, Philippe
Fraix, Valerie
Houeto, Jean-Luc
Regis, Jean
Sixel-Döring, Friederike
Pinsker, Marcus O.
Thobois, Stephane
Gharabaghi, Alireza
Stoker, Valerie
Timmermann, Lars
Schnitzler, Alfons
Krack, Paul
Vidailhet, Marie
Deuschl, Günther
KRÜGER, Rejko ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Translational Neuroscience
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