Age at onset as stratifier in idiopathic Parkinson’s disease – effect of ageing and polygenic risk score on clinical phenotypes
Abstract Several phenotypic differences observed in Parkinson’s disease (PD) patients have been linked to age at onset (AAO). We endeavoured to find out whether these differences are due to the ageing process itself by using a combined dataset of idiopathic PD (n = 430) and healthy controls (HC; n =...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-08-01
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| Series: | npj Parkinson's Disease |
| Online Access: | https://doi.org/10.1038/s41531-022-00342-7 |
| _version_ | 1797641898463068160 |
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| author | L. Pavelka A. Rauschenberger Z. Landoulsi S. Pachchek P. May E. Glaab R. Krüger on behalf of the NCER-PD Consortium |
| author_facet | L. Pavelka A. Rauschenberger Z. Landoulsi S. Pachchek P. May E. Glaab R. Krüger on behalf of the NCER-PD Consortium |
| author_sort | L. Pavelka |
| collection | DOAJ |
| description | Abstract Several phenotypic differences observed in Parkinson’s disease (PD) patients have been linked to age at onset (AAO). We endeavoured to find out whether these differences are due to the ageing process itself by using a combined dataset of idiopathic PD (n = 430) and healthy controls (HC; n = 556) excluding carriers of known PD-linked genetic mutations in both groups. We found several significant effects of AAO on motor and non-motor symptoms in PD, but when comparing the effects of age on these symptoms with HC (using age at assessment, AAA), only positive associations of AAA with burden of motor symptoms and cognitive impairment were significantly different between PD vs HC. Furthermore, we explored a potential effect of polygenic risk score (PRS) on clinical phenotype and identified a significant inverse correlation of AAO and PRS in PD. No significant association between PRS and severity of clinical symptoms was found. We conclude that the observed non-motor phenotypic differences in PD based on AAO are largely driven by the ageing process itself and not by a specific profile of neurodegeneration linked to AAO in the idiopathic PD patients. |
| first_indexed | 2024-03-11T13:52:21Z |
| format | Article |
| id | doaj.art-722493723e69462cb404f9b8182a7585 |
| institution | Directory Open Access Journal |
| issn | 2373-8057 |
| language | English |
| last_indexed | 2024-03-11T13:52:21Z |
| publishDate | 2022-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Parkinson's Disease |
| spelling | doaj.art-722493723e69462cb404f9b8182a75852023-11-02T08:11:49ZengNature Portfolionpj Parkinson's Disease2373-80572022-08-018111010.1038/s41531-022-00342-7Age at onset as stratifier in idiopathic Parkinson’s disease – effect of ageing and polygenic risk score on clinical phenotypesL. Pavelka0A. Rauschenberger1Z. Landoulsi2S. Pachchek3P. May4E. Glaab5R. Krüger6on behalf of the NCER-PD ConsortiumClinical and Experimental Neuroscience, Luxembourg Centre for Systems Biomedicine (LCSB), University of LuxembourgBiomedical Data Science Group, Luxembourg Centre for Systems Biomedicine (LCSB), University of LuxembourgBioinformatics Core, Luxembourg Centre for Systems Biomedicine (LCSB)Clinical and Experimental Neuroscience, Luxembourg Centre for Systems Biomedicine (LCSB), University of LuxembourgBioinformatics Core, Luxembourg Centre for Systems Biomedicine (LCSB)Biomedical Data Science Group, Luxembourg Centre for Systems Biomedicine (LCSB), University of LuxembourgClinical and Experimental Neuroscience, Luxembourg Centre for Systems Biomedicine (LCSB), University of LuxembourgAbstract Several phenotypic differences observed in Parkinson’s disease (PD) patients have been linked to age at onset (AAO). We endeavoured to find out whether these differences are due to the ageing process itself by using a combined dataset of idiopathic PD (n = 430) and healthy controls (HC; n = 556) excluding carriers of known PD-linked genetic mutations in both groups. We found several significant effects of AAO on motor and non-motor symptoms in PD, but when comparing the effects of age on these symptoms with HC (using age at assessment, AAA), only positive associations of AAA with burden of motor symptoms and cognitive impairment were significantly different between PD vs HC. Furthermore, we explored a potential effect of polygenic risk score (PRS) on clinical phenotype and identified a significant inverse correlation of AAO and PRS in PD. No significant association between PRS and severity of clinical symptoms was found. We conclude that the observed non-motor phenotypic differences in PD based on AAO are largely driven by the ageing process itself and not by a specific profile of neurodegeneration linked to AAO in the idiopathic PD patients.https://doi.org/10.1038/s41531-022-00342-7 |
| spellingShingle | L. Pavelka A. Rauschenberger Z. Landoulsi S. Pachchek P. May E. Glaab R. Krüger on behalf of the NCER-PD Consortium Age at onset as stratifier in idiopathic Parkinson’s disease – effect of ageing and polygenic risk score on clinical phenotypes npj Parkinson's Disease |
| title | Age at onset as stratifier in idiopathic Parkinson’s disease – effect of ageing and polygenic risk score on clinical phenotypes |
| title_full | Age at onset as stratifier in idiopathic Parkinson’s disease – effect of ageing and polygenic risk score on clinical phenotypes |
| title_fullStr | Age at onset as stratifier in idiopathic Parkinson’s disease – effect of ageing and polygenic risk score on clinical phenotypes |
| title_full_unstemmed | Age at onset as stratifier in idiopathic Parkinson’s disease – effect of ageing and polygenic risk score on clinical phenotypes |
| title_short | Age at onset as stratifier in idiopathic Parkinson’s disease – effect of ageing and polygenic risk score on clinical phenotypes |
| title_sort | age at onset as stratifier in idiopathic parkinson s disease effect of ageing and polygenic risk score on clinical phenotypes |
| url | https://doi.org/10.1038/s41531-022-00342-7 |
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