Association of polygenic risk score with response to deep brain stimulation in Parkinson’s disease
Abstract Background Deep brain stimulation (DBS) is a well-established treatment option for select patients with Parkinson’s Disease (PD). However, response to DBS varies, therefore, the ability to predict who will have better outcomes can aid patient selection. Some PD-related monogenic mutations h...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-04-01
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| Series: | BMC Neurology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12883-023-03188-5 |
| _version_ | 1797849963287281664 |
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| author | Esther Yoon Sarah Ahmed Ryan Li Sara Bandres-Ciga Cornelis Blauwendraat Irene Dustin Sonja Scholz Mark Hallett Debra Ehrlich |
| author_facet | Esther Yoon Sarah Ahmed Ryan Li Sara Bandres-Ciga Cornelis Blauwendraat Irene Dustin Sonja Scholz Mark Hallett Debra Ehrlich |
| author_sort | Esther Yoon |
| collection | DOAJ |
| description | Abstract Background Deep brain stimulation (DBS) is a well-established treatment option for select patients with Parkinson’s Disease (PD). However, response to DBS varies, therefore, the ability to predict who will have better outcomes can aid patient selection. Some PD-related monogenic mutations have been reported among factors that influence response to DBS. However, monogenic disease accounts for only a minority of patients with PD. The polygenic risk score (PRS) is an indication of cumulative genetic risk for disease. The PRS in PD has also been correlated with age of onset and symptom progression, but it is unknown whether correlations exist between PRS and DBS response. Here, we performed a pilot study to look for any such correlation. Methods We performed a retrospective analysis of 33 PD patients from the NIH PD Clinic and 13 patients from the Parkinson’s Progression Markers Initiative database who had genetic testing and underwent bilateral subthalamic nucleus DBS surgery and clinical follow-up. A PD-specific PRS was calculated for all 46 patients based on the 90 susceptibility variants identified in the latest PD genome-wide association study. We tested associations between PRS and pre- and post-surgery motor and cognitive measures using multiple regression analysis for up to two years after surgery. Results Changes in scores on the Beck Depression Inventory (BDI) were not correlated with PRS when derived from all susceptibility variants, however, when removing pathogenic and high-risk carriers from the calculation, higher PRS was significantly associated with greater reduction in BDI score at 3 months and with similar trend 24 months after DBS. PRS was not a significant predictor of Unified Parkinson’s Disease Rating Scale, Dementia Rating Scale, or phenomic and semantic fluency outcomes at 3- and 24-months after DBS surgery. Conclusions This exploratory study suggests that PRS may predict degree of improvement in depressive symptoms after DBS, though was not predictive of motor and other cognitive outcomes after DBS. Additionally, PRS may be most relevant in predicting DBS outcomes in patients lacking pathogenic or high-risk PD variants. However, this was a small preliminary study and response to DBS treatment is multifactorial, therefore, more standardized high-powered studies are needed. |
| first_indexed | 2024-04-09T18:53:47Z |
| format | Article |
| id | doaj.art-57a6aa8d89fe42aeaa690c5f30bb56b5 |
| institution | Directory Open Access Journal |
| issn | 1471-2377 |
| language | English |
| last_indexed | 2024-04-09T18:53:47Z |
| publishDate | 2023-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Neurology |
| spelling | doaj.art-57a6aa8d89fe42aeaa690c5f30bb56b52023-04-09T11:19:58ZengBMCBMC Neurology1471-23772023-04-012311610.1186/s12883-023-03188-5Association of polygenic risk score with response to deep brain stimulation in Parkinson’s diseaseEsther Yoon0Sarah Ahmed1Ryan Li2Sara Bandres-Ciga3Cornelis Blauwendraat4Irene Dustin5Sonja Scholz6Mark Hallett7Debra Ehrlich8Parkinson’s Disease Clinic, Office of the Clinical Director, National Institute of Neurological Disorders and Stroke, NIHNeurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, NIHParkinson’s Disease Clinic, Office of the Clinical Director, National Institute of Neurological Disorders and Stroke, NIHMolecular Genetics Section, Laboratory of Neurogenetics, National Institute of Aging, NIHMolecular Genetics Section, Laboratory of Neurogenetics, National Institute of Aging, NIHParkinson’s Disease Clinic, Office of the Clinical Director, National Institute of Neurological Disorders and Stroke, NIHNeurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, NIHHuman Motor Control Section, National Institute of Neurological Disorders and Stroke, NIHParkinson’s Disease Clinic, Office of the Clinical Director, National Institute of Neurological Disorders and Stroke, NIHAbstract Background Deep brain stimulation (DBS) is a well-established treatment option for select patients with Parkinson’s Disease (PD). However, response to DBS varies, therefore, the ability to predict who will have better outcomes can aid patient selection. Some PD-related monogenic mutations have been reported among factors that influence response to DBS. However, monogenic disease accounts for only a minority of patients with PD. The polygenic risk score (PRS) is an indication of cumulative genetic risk for disease. The PRS in PD has also been correlated with age of onset and symptom progression, but it is unknown whether correlations exist between PRS and DBS response. Here, we performed a pilot study to look for any such correlation. Methods We performed a retrospective analysis of 33 PD patients from the NIH PD Clinic and 13 patients from the Parkinson’s Progression Markers Initiative database who had genetic testing and underwent bilateral subthalamic nucleus DBS surgery and clinical follow-up. A PD-specific PRS was calculated for all 46 patients based on the 90 susceptibility variants identified in the latest PD genome-wide association study. We tested associations between PRS and pre- and post-surgery motor and cognitive measures using multiple regression analysis for up to two years after surgery. Results Changes in scores on the Beck Depression Inventory (BDI) were not correlated with PRS when derived from all susceptibility variants, however, when removing pathogenic and high-risk carriers from the calculation, higher PRS was significantly associated with greater reduction in BDI score at 3 months and with similar trend 24 months after DBS. PRS was not a significant predictor of Unified Parkinson’s Disease Rating Scale, Dementia Rating Scale, or phenomic and semantic fluency outcomes at 3- and 24-months after DBS surgery. Conclusions This exploratory study suggests that PRS may predict degree of improvement in depressive symptoms after DBS, though was not predictive of motor and other cognitive outcomes after DBS. Additionally, PRS may be most relevant in predicting DBS outcomes in patients lacking pathogenic or high-risk PD variants. However, this was a small preliminary study and response to DBS treatment is multifactorial, therefore, more standardized high-powered studies are needed.https://doi.org/10.1186/s12883-023-03188-5Deep brain stimulationParkinson’s diseasePolygenic risk score |
| spellingShingle | Esther Yoon Sarah Ahmed Ryan Li Sara Bandres-Ciga Cornelis Blauwendraat Irene Dustin Sonja Scholz Mark Hallett Debra Ehrlich Association of polygenic risk score with response to deep brain stimulation in Parkinson’s disease BMC Neurology Deep brain stimulation Parkinson’s disease Polygenic risk score |
| title | Association of polygenic risk score with response to deep brain stimulation in Parkinson’s disease |
| title_full | Association of polygenic risk score with response to deep brain stimulation in Parkinson’s disease |
| title_fullStr | Association of polygenic risk score with response to deep brain stimulation in Parkinson’s disease |
| title_full_unstemmed | Association of polygenic risk score with response to deep brain stimulation in Parkinson’s disease |
| title_short | Association of polygenic risk score with response to deep brain stimulation in Parkinson’s disease |
| title_sort | association of polygenic risk score with response to deep brain stimulation in parkinson s disease |
| topic | Deep brain stimulation Parkinson’s disease Polygenic risk score |
| url | https://doi.org/10.1186/s12883-023-03188-5 |
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