Category: Parkinson's Disease: Genetics
Objective: We identified (Weiss et al., 2016) that single nucleotide polymorphism (SNPs) of the alpha-synuclein gene (SNCA) predicted the motor effect of subthalamic nucleus stimulation (STN-DBS) on sporadic Parkinson’s disease (PD) patients two years from surgery compared to the preoperative baseline. We aimed to replicate these findings in an independent cohort. In additional exploratory analyses, we studied if other PD risk and progression variants from the latest GWAS are associated with therapeutic outcome.
Background: Treatment decisions on STN-DBS in PD are highly complex and depend on various motor and non-motor determinants. Outcome predictors considering individual biology and genetic architecture of PD are unknown but warranted to obtain fine-grained treatment decisions.
Method: We comprehensively genotyped 173 patients from the EarlyStim cohort using NeuroChip (89 with best medical treatment (BMT) and 84 with STN-DBS), and assessed the clinico-genetic associations with longitudinal outcome (UPDRS-I to IV and quality of life PDQ-39).
Results: The EarlyStim cohort differed in clinical characteristics from the original cohort, including preoperative UPDRS III in MedOff and disease duration. In the EarlyStim cohort, 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.
Conclusion: 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.
References: D. Weiss, S. Herrmann, L. Wang, C. Schulte, K. Brockmann, C. Plewnia, T. Gasser, M. Sharma, A. Gharabaghi, R. Krüger, Alpha-synuclein gene variants may predict neurostimulation outcome: Genetic Predictors of Neurostimulation Outcome, Mov Disord. 31 (2016) 601–603.
To cite this abstract in AMA style:
D. Weiss, Z. Landoulsi, P. May, M. Sharma, M. Schüpbach, H. You, JC. Corvol, S. Paschen, AK. Helmers, M. Barbe, G. Fink, A. Kühn, C. Brefel-Courbon, L. Wojtecki, P. Damier, V. Fraix, JL. Houeto, J. Regis, F. Sixel-Döring, M. Pinsker, S. Thobois, A. Gharabaghi, V. Stoker, L. Timmermann, A. Schnitzler, P. Krack, M. Vidailhet, G. Deuschl, R. Krüger. Genetic stratification of motor and quality of life outcomes in Parkinson’s disease in the EARLYSTIM study [abstract]. Mov Disord. 2022; 37 (suppl 2). https://www.mdsabstracts.org/abstract/genetic-stratification-of-motor-and-quality-of-life-outcomes-in-parkinsons-disease-in-the-earlystim-study/. Accessed June 14, 2025.« Back to 2022 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/genetic-stratification-of-motor-and-quality-of-life-outcomes-in-parkinsons-disease-in-the-earlystim-study/