Genetic stratification of motor and QoL outcomes in Parkinson's disease in the EARLYSTIM study

Daniel Weiss*, Zied Landoulsi, Patrick May, Manu Sharma, Michael Schüpbach, Hana You, Jean Christophe Corvol, Steffen Paschen, Ann Kristin Helmers, Michael Barbe, Gereon Fink, Andrea A. Kühn, Christine Brefel Courbon, Lars Wojtecki, Philippe Damier, Valerie Fraix, Jean Luc Houeto, Jean Regis, Friederike Sixel-Döring, Marcus O. PinskerStephane Thobois, Alireza Gharabaghi, Valerie Stoker, Lars Timmermann, Alfons Schnitzler, Paul Krack, Marie Vidailhet, Günther Deuschl, Rejko Krüger

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)169-174
Number of pages6
JournalParkinsonism and Related Disorders
Volume103
Early online date8 Sep 2022
DOIs
Publication statusPublished - Oct 2022

Keywords

  • Alpha-synuclein
  • Deep brain stimulation
  • Genetic association
  • Parkinson's disease

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