Relevance of genetic testing in the gene-targeted trial era: the Rostock Parkinson’s disease study

Parkinson’s disease; Genetic testing; Next-generation sequencing

Detalles Bibliográficos
Autores: Westenberger, Ana, Skrahina, Volha, Usnich, Tatiana, Beetz, Christian, Vollstedt, Eva-Juliane, Laabs, Björn-Hergen, HERNANDEZ-VARA, JORGE
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:11351/12013
Acceso en línea:https://hdl.handle.net/11351/12013
http://hdl.handle.net/11351/12013
Access Level:acceso abierto
Palabra clave:Anomalies cromosòmiques
Parkinson, Malaltia de - Aspectes genètics
Cromosomes humans - Anomalies - Diagnòstic
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Genetic Testing
DISEASES::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Basal Ganglia Diseases::Parkinsonian Disorders::Parkinson Disease
Other subheadings::Other subheadings::Other subheadings::/genetics
PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::técnicas y procedimientos diagnósticos::técnicas de laboratorio clínico::pruebas genéticas
ENFERMEDADES::enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::enfermedades de los ganglios basales::trastornos parkinsonianos::enfermedad de Parkinson
Otros calificadores::Otros calificadores::Otros calificadores::/genética
FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación
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oai_identifier_str oai:recercat.cat:11351/12013
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Relevance of genetic testing in the gene-targeted trial era: the Rostock Parkinson’s disease study
title Relevance of genetic testing in the gene-targeted trial era: the Rostock Parkinson’s disease study
spellingShingle Relevance of genetic testing in the gene-targeted trial era: the Rostock Parkinson’s disease study
Westenberger, Ana
Anomalies cromosòmiques
Parkinson, Malaltia de - Aspectes genètics
Cromosomes humans - Anomalies - Diagnòstic
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Genetic Testing
DISEASES::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Basal Ganglia Diseases::Parkinsonian Disorders::Parkinson Disease
Other subheadings::Other subheadings::Other subheadings::/genetics
PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::técnicas y procedimientos diagnósticos::técnicas de laboratorio clínico::pruebas genéticas
ENFERMEDADES::enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::enfermedades de los ganglios basales::trastornos parkinsonianos::enfermedad de Parkinson
Otros calificadores::Otros calificadores::Otros calificadores::/genética
FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación
title_short Relevance of genetic testing in the gene-targeted trial era: the Rostock Parkinson’s disease study
title_full Relevance of genetic testing in the gene-targeted trial era: the Rostock Parkinson’s disease study
title_fullStr Relevance of genetic testing in the gene-targeted trial era: the Rostock Parkinson’s disease study
title_full_unstemmed Relevance of genetic testing in the gene-targeted trial era: the Rostock Parkinson’s disease study
title_sort Relevance of genetic testing in the gene-targeted trial era: the Rostock Parkinson’s disease study
dc.creator.none.fl_str_mv Westenberger, Ana
Skrahina, Volha
Usnich, Tatiana
Beetz, Christian
Vollstedt, Eva-Juliane
Laabs, Björn-Hergen
HERNANDEZ-VARA, JORGE
author Westenberger, Ana
author_facet Westenberger, Ana
Skrahina, Volha
Usnich, Tatiana
Beetz, Christian
Vollstedt, Eva-Juliane
Laabs, Björn-Hergen
HERNANDEZ-VARA, JORGE
author_role author
author2 Skrahina, Volha
Usnich, Tatiana
Beetz, Christian
Vollstedt, Eva-Juliane
Laabs, Björn-Hergen
HERNANDEZ-VARA, JORGE
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Institut Català de la Salut
[Westenberger A, Usnich T, Vollstedt EJ] Institute of Neurogenetics, University of Lübeck, University Medical Center Schleswig-Holstein, Lübeck, Schleswig-Holstein, Germany. [Skrahina V, Beetz C] CENTOGENE GmbH, Rostock, Mecklenburg-Vorpommern, Germany. [Laabs BH] Institute of Medical Biometry and Statistics, University of Lübeck, University Medical Center Schleswig-Holstein, Lübeck, Schleswig-Holstein, Germany. [Hernández-Vara J] Servei de Neurologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain
Vall d'Hebron Barcelona Hospital Campus
dc.subject.none.fl_str_mv Anomalies cromosòmiques
Parkinson, Malaltia de - Aspectes genètics
Cromosomes humans - Anomalies - Diagnòstic
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Genetic Testing
DISEASES::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Basal Ganglia Diseases::Parkinsonian Disorders::Parkinson Disease
Other subheadings::Other subheadings::Other subheadings::/genetics
PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::técnicas y procedimientos diagnósticos::técnicas de laboratorio clínico::pruebas genéticas
ENFERMEDADES::enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::enfermedades de los ganglios basales::trastornos parkinsonianos::enfermedad de Parkinson
Otros calificadores::Otros calificadores::Otros calificadores::/genética
FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación
topic Anomalies cromosòmiques
Parkinson, Malaltia de - Aspectes genètics
Cromosomes humans - Anomalies - Diagnòstic
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Genetic Testing
DISEASES::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Basal Ganglia Diseases::Parkinsonian Disorders::Parkinson Disease
Other subheadings::Other subheadings::Other subheadings::/genetics
PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::técnicas y procedimientos diagnósticos::técnicas de laboratorio clínico::pruebas genéticas
ENFERMEDADES::enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::enfermedades de los ganglios basales::trastornos parkinsonianos::enfermedad de Parkinson
Otros calificadores::Otros calificadores::Otros calificadores::/genética
FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación
description Parkinson’s disease; Genetic testing; Next-generation sequencing
publishDate 2024
dc.date.none.fl_str_mv 2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11351/12013
http://hdl.handle.net/11351/12013
url https://hdl.handle.net/11351/12013
http://hdl.handle.net/11351/12013
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Brain;147(8)
https://doi.org/10.1093/brain/awae188
dc.rights.none.fl_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv Scientia
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869423901177544704
spelling Relevance of genetic testing in the gene-targeted trial era: the Rostock Parkinson’s disease studyWestenberger, AnaSkrahina, VolhaUsnich, TatianaBeetz, ChristianVollstedt, Eva-JulianeLaabs, Björn-HergenHERNANDEZ-VARA, JORGEAnomalies cromosòmiquesParkinson, Malaltia de - Aspectes genèticsCromosomes humans - Anomalies - DiagnòsticANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Genetic TestingDISEASES::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Basal Ganglia Diseases::Parkinsonian Disorders::Parkinson DiseaseOther subheadings::Other subheadings::Other subheadings::/geneticsPHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::MutationTÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::técnicas y procedimientos diagnósticos::técnicas de laboratorio clínico::pruebas genéticasENFERMEDADES::enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::enfermedades de los ganglios basales::trastornos parkinsonianos::enfermedad de ParkinsonOtros calificadores::Otros calificadores::Otros calificadores::/genéticaFENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutaciónParkinson’s disease; Genetic testing; Next-generation sequencingEnfermedad de Parkinson; Pruebas genéticas; Secuenciación de nueva generaciónMalaltia de Parkinson; Proves genètiques; Seqüenciació de nova generacióEstimates of the spectrum and frequency of pathogenic variants in Parkinson’s disease (PD) in different populations are currently limited and biased. Furthermore, although therapeutic modification of several genetic targets has reached the clinical trial stage, a major obstacle in conducting these trials is that PD patients are largely unaware of their genetic status and, therefore, cannot be recruited. Expanding the number of investigated PD-related genes and including genes related to disorders with overlapping clinical features in large, well-phenotyped PD patient groups is a prerequisite for capturing the full variant spectrum underlying PD and for stratifying and prioritizing patients for gene-targeted clinical trials. The Rostock Parkinson’s disease (ROPAD) study is an observational clinical study aiming to determine the frequency and spectrum of genetic variants contributing to PD in a large international cohort. We investigated variants in 50 genes with either an established relevance for PD or possible phenotypic overlap in a group of 12 580 PD patients from 16 countries [62.3% male; 92.0% White; 27.0% positive family history (FH+), median age at onset (AAO) 59 years] using a next-generation sequencing panel. Altogether, in 1864 (14.8%) ROPAD participants (58.1% male; 91.0% White, 35.5% FH+, median AAO 55 years), a PD-relevant genetic test (PDGT) was positive based on GBA1 risk variants (10.4%) or pathogenic/likely pathogenic variants in LRRK2 (2.9%), PRKN (0.9%), SNCA (0.2%) or PINK1 (0.1%) or a combination of two genetic findings in two genes (∼0.2%). Of note, the adjusted positive PDGT fraction, i.e. the fraction of positive PDGTs per country weighted by the fraction of the population of the world that they represent, was 14.5%. Positive PDGTs were identified in 19.9% of patients with an AAO ≤ 50 years, in 19.5% of patients with FH+ and in 26.9% with an AAO ≤ 50 years and FH+. In comparison to the idiopathic PD group (6846 patients with benign variants), the positive PDGT group had a significantly lower AAO (4 years, P = 9 × 10−34). The probability of a positive PDGT decreased by 3% with every additional AAO year (P = 1 × 10−35). Female patients were 22% more likely to have a positive PDGT (P = 3 × 10−4), and for individuals with FH+ this likelihood was 55% higher (P = 1 × 10−14). About 0.8% of the ROPAD participants had positive genetic testing findings in parkinsonism-, dystonia/dyskinesia- or dementia-related genes. In the emerging era of gene-targeted PD clinical trials, our finding that ∼15% of patients harbour potentially actionable genetic variants offers an important prospect to affected individuals and their families and underlines the need for genetic testing in PD patients. Thus, the insights from the ROPAD study allow for data-driven, differential genetic counselling across the spectrum of different AAOs and family histories and promote a possible policy change in the application of genetic testing as a routine part of patient evaluation and care in PD.Denali Therapeutics Inc. (South San Francisco, CA) partially funded laboratory testing services to CENTOGENE GmbH.Oxford University PressInstitut Català de la Salut[Westenberger A, Usnich T, Vollstedt EJ] Institute of Neurogenetics, University of Lübeck, University Medical Center Schleswig-Holstein, Lübeck, Schleswig-Holstein, Germany. [Skrahina V, Beetz C] CENTOGENE GmbH, Rostock, Mecklenburg-Vorpommern, Germany. [Laabs BH] Institute of Medical Biometry and Statistics, University of Lübeck, University Medical Center Schleswig-Holstein, Lübeck, Schleswig-Holstein, Germany. [Hernández-Vara J] Servei de Neurologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, SpainVall d'Hebron Barcelona Hospital Campus202420242024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/11351/12013http://hdl.handle.net/11351/12013Scientiareponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésBrain;147(8)https://doi.org/10.1093/brain/awae188Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:11351/120132026-05-29T05:05:01Z
score 15,198674

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