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

Daniel Weiss¹, Zied Landoulsi², Patrick May², Manu Sharma³, Michael Schüpbach⁴, Hana You⁵, Jean Christophe Corvol⁶, Steffen Paschen⁷, Ann-Kristin Helmers⁸, Michael Barbe⁹, Gereon Fink¹⁰, Andrea A Kühn¹¹, Christine Brefel Courbon¹², Lars Wojtecki¹³, Philippe Damier¹⁴, Valerie Fraix¹⁵, Jean-Luc Houeto¹⁶, Jean Regis¹⁷, Friederike Sixel-Döring¹⁸, Marcus O Pinsker¹⁹, Stephane Thobois²⁰, Alireza Gharabaghi²¹, Valerie Stoker²², Lars Timmermann²³, Alfons Schnitzler¹², Paul Krack²⁴, Marie Vidailhet⁴, Günther Deuschl⁷, Rejko Krüger²⁵

Affiliations

¹ Centre for Neurology, Department for Neurodegenerative Disease, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. Electronic address: daniel.weiss@uni-tuebingen.de.
² Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg.
³ Centre for Genetic Epidemiology, Institute for Clinical Epidemiology and Applied Biometry, University of Tübingen, Tübingen, Germany.
⁴ Département de Neurologie, Hôpital Pitié-Salpêtrière, Centre d'Investigation Clinique 1422, Institut du Cerveau et de la Moelle Epinière, Institut National de Santé et en Recherche Médicale, Assistance Publique Hôpitaux de Paris, France; Institute of Neurology, Konolfingen, Switzerland; Department of Neurology, University Hospital Bern and University of Bern, Switzerland.
⁵ Department of Neurology, Inselspital University Hospital Bern and University of Bern, Switzerland.
⁶ Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, UMR 1127, Inserm 1127, CNRS7225, AP-HP, Department of Neurology, Salpetriere University Hospital, Paris, France.
⁷ Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Assistance Publique Hôpitaux de paris, Department of Neurology, Pitié-Salpêtrière Hospital, Paris, France.
⁸ Department of Neurology, UKSH, Kiel Campus Christian-Albrechts-University, Kiel, Germany.
⁹ Department of Neurosurgery, UKSH Kiel, Kiel Campus Christian-Albrechts-University, Kiel, Germany.
¹⁰ Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; Cognitive Neuroscience, Institute of Neuroscience and Medicine, Research Centre Jülich, Germany.
¹¹ Department of Neurology, Charité-Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany.
¹² Department of Neurology, INSERM Unite 1214, University Hospital Toulouse, France.
¹³ Institute of Clinical Neuroscience and Medical Psychology, Department of Neurology, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.
¹⁴ CHU Nantes, INSERM, CIC1413, Hôpital Laënnec, Nantes, France.
¹⁵ Univ. Grenoble Alpes, Inserm, U1216, CHU Grenoble Alpes, Grenoble Institut Neurosciences, 38000, Grenoble, France.
¹⁶ Department of Neurology, INSERM, Univ. Limoges, CHU Limoges, IRD, U1094 Tropical Neuroepidemiology, Institute of Epidemiology and Tropical Neurology, GEIST, Limoges, France.
¹⁷ Aix Marseille University Department of Functional Neurosurgery, CHU Timone, APHM, Marseille, France.
¹⁸ Paracelsus-Elena-Klinik Kassel, Kassel, Germany.
¹⁹ Division of Stereotactic and Functional Neurosurgery, University Medical Center, Freiburg, Freiburg, Germany.
²⁰ Hospices Civils de Lyon, Hôpital Neurologique Pierre Wertheimer, Service de Neurologie C, Centre Expert Parkinson, Bron, France, France; Université Lyon, Université Claude Bernard Lyon 1, Faculté de Médecine Lyon Sud Charles Mérieux, Oullins, France.
²¹ Institute for Neuromodulation and Neurotechnology, University of Tübingen, Tübingen, Germany.
²² Medtronic, Minneapolis, MN, USA.
²³ Department of Neurology, University Hospital Marburg, Marburg, Germany.
²⁴ Department of Neurology, Bern University Hospital and University of Bern, Bern, Switzerland.
²⁵ Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg; Transversal Translational Medicine, Luxembourg Institute of Health, Strassen, Luxembourg; Parkinson Research Clinic, Centre Hospitalier de Luxembourg, Luxembourg.

PMID: 36117018
DOI: 10.1016/j.parkreldis.2022.08.025

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

Daniel Weiss et al. Parkinsonism Relat Disord. 2022 Oct.

. 2022 Oct:103:169-174.

doi: 10.1016/j.parkreldis.2022.08.025. Epub 2022 Sep 8.

Authors

Affiliations

¹ Centre for Neurology, Department for Neurodegenerative Disease, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. Electronic address: daniel.weiss@uni-tuebingen.de.
² Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg.
³ Centre for Genetic Epidemiology, Institute for Clinical Epidemiology and Applied Biometry, University of Tübingen, Tübingen, Germany.
⁴ Département de Neurologie, Hôpital Pitié-Salpêtrière, Centre d'Investigation Clinique 1422, Institut du Cerveau et de la Moelle Epinière, Institut National de Santé et en Recherche Médicale, Assistance Publique Hôpitaux de Paris, France; Institute of Neurology, Konolfingen, Switzerland; Department of Neurology, University Hospital Bern and University of Bern, Switzerland.
⁵ Department of Neurology, Inselspital University Hospital Bern and University of Bern, Switzerland.
⁶ Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, UMR 1127, Inserm 1127, CNRS7225, AP-HP, Department of Neurology, Salpetriere University Hospital, Paris, France.
⁷ Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Assistance Publique Hôpitaux de paris, Department of Neurology, Pitié-Salpêtrière Hospital, Paris, France.
⁸ Department of Neurology, UKSH, Kiel Campus Christian-Albrechts-University, Kiel, Germany.
⁹ Department of Neurosurgery, UKSH Kiel, Kiel Campus Christian-Albrechts-University, Kiel, Germany.
¹⁰ Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; Cognitive Neuroscience, Institute of Neuroscience and Medicine, Research Centre Jülich, Germany.
¹¹ Department of Neurology, Charité-Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany.
¹² Department of Neurology, INSERM Unite 1214, University Hospital Toulouse, France.
¹³ Institute of Clinical Neuroscience and Medical Psychology, Department of Neurology, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.
¹⁴ CHU Nantes, INSERM, CIC1413, Hôpital Laënnec, Nantes, France.
¹⁵ Univ. Grenoble Alpes, Inserm, U1216, CHU Grenoble Alpes, Grenoble Institut Neurosciences, 38000, Grenoble, France.
¹⁶ Department of Neurology, INSERM, Univ. Limoges, CHU Limoges, IRD, U1094 Tropical Neuroepidemiology, Institute of Epidemiology and Tropical Neurology, GEIST, Limoges, France.
¹⁷ Aix Marseille University Department of Functional Neurosurgery, CHU Timone, APHM, Marseille, France.
¹⁸ Paracelsus-Elena-Klinik Kassel, Kassel, Germany.
¹⁹ Division of Stereotactic and Functional Neurosurgery, University Medical Center, Freiburg, Freiburg, Germany.
²⁰ Hospices Civils de Lyon, Hôpital Neurologique Pierre Wertheimer, Service de Neurologie C, Centre Expert Parkinson, Bron, France, France; Université Lyon, Université Claude Bernard Lyon 1, Faculté de Médecine Lyon Sud Charles Mérieux, Oullins, France.
²¹ Institute for Neuromodulation and Neurotechnology, University of Tübingen, Tübingen, Germany.
²² Medtronic, Minneapolis, MN, USA.
²³ Department of Neurology, University Hospital Marburg, Marburg, Germany.
²⁴ Department of Neurology, Bern University Hospital and University of Bern, Bern, Switzerland.
²⁵ Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg; Transversal Translational Medicine, Luxembourg Institute of Health, Strassen, Luxembourg; Parkinson Research Clinic, Centre Hospitalier de Luxembourg, Luxembourg.

PMID: 36117018
DOI: 10.1016/j.parkreldis.2022.08.025

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.

Keywords: Alpha-synuclein; Deep brain stimulation; Genetic association; Parkinson's disease.

PubMed Disclaimer

Comment in

Steering the genes into the field of deep brain stimulation.
Salles PA, Mata IF. Salles PA, et al. Parkinsonism Relat Disord. 2022 Oct;103:166-168. doi: 10.1016/j.parkreldis.2022.09.006. Epub 2022 Sep 12. Parkinsonism Relat Disord. 2022. PMID: 36109294 No abstract available.

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions

LinkOut - more resources

Full Text Sources
- ClinicalKey
- Elsevier Science
Medical
- MedlinePlus Health Information
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Affiliations

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

Authors

Affiliations

Abstract

Comment in

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous