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Genetic architecture of Parkinson’s disease subtypes – Review of the literature

The heterogeneity of Parkinson’s disease (PD) has been recognized since its description by James Parkinson over 200 years ago. The complexity of motor and non-motor PD manifestations has led to many attempts of PD subtyping with different prognostic outcomes; however, the pathophysiological foundati...

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Autores principales: Dulski, Jarosław, Uitti, Ryan J., Ross, Owen A., Wszolek, Zbigniew K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9632166/
https://www.ncbi.nlm.nih.gov/pubmed/36337703
http://dx.doi.org/10.3389/fnagi.2022.1023574
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author Dulski, Jarosław
Uitti, Ryan J.
Ross, Owen A.
Wszolek, Zbigniew K.
author_facet Dulski, Jarosław
Uitti, Ryan J.
Ross, Owen A.
Wszolek, Zbigniew K.
author_sort Dulski, Jarosław
collection PubMed
description The heterogeneity of Parkinson’s disease (PD) has been recognized since its description by James Parkinson over 200 years ago. The complexity of motor and non-motor PD manifestations has led to many attempts of PD subtyping with different prognostic outcomes; however, the pathophysiological foundations of PD heterogeneity remain elusive. Genetic contributions to PD may be informative in understanding the underpinnings of PD subtypes. As such, recognizing genotype-phenotype associations may be crucial for successful gene therapy. We review the state of knowledge on the genetic architecture underlying PD subtypes, discussing the monogenic forms, as well as oligo- and polygenic risk factors associated with various PD subtypes. Based on our review, we argue for the unification of PD subtyping classifications, the dichotomy of studies on genetic factors and genetic modifiers of PD, and replication of results from previous studies.
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spelling pubmed-96321662022-11-04 Genetic architecture of Parkinson’s disease subtypes – Review of the literature Dulski, Jarosław Uitti, Ryan J. Ross, Owen A. Wszolek, Zbigniew K. Front Aging Neurosci Neuroscience The heterogeneity of Parkinson’s disease (PD) has been recognized since its description by James Parkinson over 200 years ago. The complexity of motor and non-motor PD manifestations has led to many attempts of PD subtyping with different prognostic outcomes; however, the pathophysiological foundations of PD heterogeneity remain elusive. Genetic contributions to PD may be informative in understanding the underpinnings of PD subtypes. As such, recognizing genotype-phenotype associations may be crucial for successful gene therapy. We review the state of knowledge on the genetic architecture underlying PD subtypes, discussing the monogenic forms, as well as oligo- and polygenic risk factors associated with various PD subtypes. Based on our review, we argue for the unification of PD subtyping classifications, the dichotomy of studies on genetic factors and genetic modifiers of PD, and replication of results from previous studies. Frontiers Media S.A. 2022-10-20 /pmc/articles/PMC9632166/ /pubmed/36337703 http://dx.doi.org/10.3389/fnagi.2022.1023574 Text en Copyright © 2022 Dulski, Uitti, Ross and Wszolek. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Dulski, Jarosław
Uitti, Ryan J.
Ross, Owen A.
Wszolek, Zbigniew K.
Genetic architecture of Parkinson’s disease subtypes – Review of the literature
title Genetic architecture of Parkinson’s disease subtypes – Review of the literature
title_full Genetic architecture of Parkinson’s disease subtypes – Review of the literature
title_fullStr Genetic architecture of Parkinson’s disease subtypes – Review of the literature
title_full_unstemmed Genetic architecture of Parkinson’s disease subtypes – Review of the literature
title_short Genetic architecture of Parkinson’s disease subtypes – Review of the literature
title_sort genetic architecture of parkinson’s disease subtypes – review of the literature
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9632166/
https://www.ncbi.nlm.nih.gov/pubmed/36337703
http://dx.doi.org/10.3389/fnagi.2022.1023574
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