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

Westenberger, Ana; Skrahina, Volha; Usnich, Tatiana; Beetz, Christian; Vollstedt, Eva-Juliane; Laabs, Björn-Hergen; Paul, Jefri J; Curado, Filipa; Skobalj, Snezana; Gaber, Hanaa; Olmedillas, Maria; Morgan, John C; Mullin, Stephen; Dos Santos Ghilardi, Maria Gabriela; Pulera, Mark; Musacchio, Thomas; Myers, Bennett; Negrotti, Anna; Pal, Gian; Pavese, Nicola; Raw, Jason; Balck, Alexander; Reetz, Kathrin; Reiner, Johnathan; Lohmann, Katja; Stathis, Pantelis; Rosenberg, David; Ruiz-Lopez, Marta; Bogdanovic, Xenia; Tönges, Lars; Ruiz Martinez, Javier; Sammler, Esther; Hanssen, Henrike; Santos-Lobato, Bruno Lopes; Saunders-Pullman, Rachel; Schlesinger, Ilana; Schofield, Christine M; Stocchi, Fabrizio; Kasten, Meike; Schumacher-Schuh, Artur F; Scott, Burton; Sesar Ignacio, Ángel; Shafer, Stuart J; Pinto De Souza, Carolina; Toschi, Giulia; Ameziane, Najim; Sheridan, Ray; Silverdale, Monty; Tagliati, Michele; Tai, Yen F; Tumas, Vitor; Urban, Peter Paul; Vacca, Laura; Crosiers, David; Afshari, Mitra; Vandenberghe, Wim; Valente, Enza Maria; Djaldetti, Ruth; Brüggemann, Norbert; Valzania, Franco; Vela-Desojo, Lydia; Weill, Caroline; Aasly, Jan Olav; Weise, David; Wojcieszek, Joanne; Borsche, Max; Cullufi, Paskal; Wolz, Martin; Yahalom, Gilad; Yalcin-Cakmakli, Gul; Zittel, Simone; Rolfs, Arndt; Dogu, Okan; Zlotnik, Yair; Kandaswamy, Krishna K; Lange, Lara M; Csoti, Ilona; Klein, Christine; Bauer, Peter; Agarwal, Pinky; Hassin-Baer, Sharon; Aldred, Jason; Alonso-Frech, Fernando; Hu, Michele T; Dashtipour, Khashayar; Anderson, Roderick; Araújo, Rui; Arkadir, David; Eggers, Carsten; Avenali, Micol; Balal, Mehmet; Hauser, Robert A; Benizri, Sandra; Bette, Sagari; Bhatia, Perminder; Bonello, Michael; Demirkiran, Meltem; Hummelgen, Eduardo; Braga-Neto, Pedro; Brauneis, Sarah; Cardoso, Francisco Eduardo Costa; Cavallieri, Francesco; Schell, Nathalie; Elibol, Bulent; Classen, Joseph; Cohen, Lisa; Coletta, Della; De Carvalho Aguiar, Patricia; De Rosa, Anna; Ellenbogen, Aaron; Ertan, Sibel; Fabiani, Giorgio; Nieves, Anette; Hernández-Vara, Jorge; Falkenburger, Björn H; Farrow, Simon; Percesepe, Antonio; Hussey, Kelly; Fay-Karmon, Tsviya; Ferencz, Gerald J; Fonoff, Erich Talamoni; Fragoso, Yara Dadalti; Genç, Gençer; Gorospe, Arantza; Herting, Birgit; Nitsan, Zeev; Grandas, Francisco; Gruber, Doreen; Gudesblatt, Mark; Gurevich, Tanya; Infante, Jon; Piccoli, Tommaso; Hagenah, Johann; Hanagasi, Hasmet A; Hinson, Vanessa K; Hogg, Elliot; Isaacson, Stuart H; Jaumà, Serge; Koleva-Alazeh, Natalia; Sophia, Rani; Kuhlenbäumer, Gregor; Kühn, Andrea; Terwecoren, Annelies; Oskooilar, Nader; Litvan, Irene; López-Manzanares, Lydia; Luxmore, Mckenzie; Prell, Tino; Manandhar, Sujeena; Marcaud, Veronique; Spitz, Mariana; Markopoulou, Katerina; Marras, Connie; Mckenzie, Mark; Matarazzo, Michele; Öztop-Çakmak, Özgür; Thonke, Sven; Merello, Marcelo; Mollenhauer, Brit

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

Estimates 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 th...

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Autores:	Westenberger, Ana, Skrahina, Volha, Usnich, Tatiana, Beetz, Christian, Vollstedt, Eva-Juliane, Laabs, Björn-Hergen, Paul, Jefri J, Curado, Filipa, Skobalj, Snezana, Gaber, Hanaa, Olmedillas, Maria, Morgan, John C, Mullin, Stephen, Dos Santos Ghilardi, Maria Gabriela, Pulera, Mark, Musacchio, Thomas, Myers, Bennett, Negrotti, Anna, Pal, Gian, Pavese, Nicola, Raw, Jason, Balck, Alexander, Reetz, Kathrin, Reiner, Johnathan, Lohmann, Katja, Stathis, Pantelis, Rosenberg, David, Ruiz-Lopez, Marta, Bogdanovic, Xenia, Tönges, Lars, Ruiz Martinez, Javier, Sammler, Esther, Hanssen, Henrike, Santos-Lobato, Bruno Lopes, Saunders-Pullman, Rachel, Schlesinger, Ilana, Schofield, Christine M, Stocchi, Fabrizio, Kasten, Meike, Schumacher-Schuh, Artur F, Scott, Burton, Sesar Ignacio, Ángel, Shafer, Stuart J, Pinto De Souza, Carolina, Toschi, Giulia, Ameziane, Najim, Sheridan, Ray, Silverdale, Monty, Tagliati, Michele, Tai, Yen F, Tumas, Vitor, Urban, Peter Paul, Vacca, Laura, Crosiers, David, Afshari, Mitra, Vandenberghe, Wim, Valente, Enza Maria, Djaldetti, Ruth, Brüggemann, Norbert, Valzania, Franco, Vela-Desojo, Lydia, Weill, Caroline, Aasly, Jan Olav, Weise, David, Wojcieszek, Joanne, Borsche, Max, Cullufi, Paskal, Wolz, Martin, Yahalom, Gilad, Yalcin-Cakmakli, Gul, Zittel, Simone, Rolfs, Arndt, Dogu, Okan, Zlotnik, Yair, Kandaswamy, Krishna K, Lange, Lara M, Csoti, Ilona, Klein, Christine, Bauer, Peter, Agarwal, Pinky, Hassin-Baer, Sharon, Aldred, Jason, Alonso-Frech, Fernando, Hu, Michele T, Dashtipour, Khashayar, Anderson, Roderick, Araújo, Rui, Arkadir, David, Eggers, Carsten, Avenali, Micol, Balal, Mehmet, Hauser, Robert A, Benizri, Sandra, Bette, Sagari, Bhatia, Perminder, Bonello, Michael, Demirkiran, Meltem, Hummelgen, Eduardo, Braga-Neto, Pedro, Brauneis, Sarah, Cardoso, Francisco Eduardo Costa, Cavallieri, Francesco, Schell, Nathalie, Elibol, Bulent, Classen, Joseph, Cohen, Lisa, Coletta, Della, De Carvalho Aguiar, Patricia, De Rosa, Anna, Ellenbogen, Aaron, Ertan, Sibel, Fabiani, Giorgio, Nieves, Anette, Hernández-Vara, Jorge, Falkenburger, Björn H, Farrow, Simon, Percesepe, Antonio, Hussey, Kelly, Fay-Karmon, Tsviya, Ferencz, Gerald J, Fonoff, Erich Talamoni, Fragoso, Yara Dadalti, Genç, Gençer, Gorospe, Arantza, Herting, Birgit, Nitsan, Zeev, Grandas, Francisco, Gruber, Doreen, Gudesblatt, Mark, Gurevich, Tanya, Infante, Jon, Piccoli, Tommaso, Hagenah, Johann, Hanagasi, Hasmet A, Hinson, Vanessa K, Hogg, Elliot, Isaacson, Stuart H, Jaumà, Serge, Koleva-Alazeh, Natalia, Sophia, Rani, Kuhlenbäumer, Gregor, Kühn, Andrea, Terwecoren, Annelies, Oskooilar, Nader, Litvan, Irene, López-Manzanares, Lydia, Luxmore, Mckenzie, Prell, Tino, Manandhar, Sujeena, Marcaud, Veronique, Spitz, Mariana, Markopoulou, Katerina, Marras, Connie, Mckenzie, Mark, Matarazzo, Michele, Öztop-Çakmak, Özgür, Thonke, Sven, Merello, Marcelo, Mollenhauer, Brit
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:2445/215720
Acceso en línea:	https://hdl.handle.net/2445/215720
Access Level:	acceso abierto
Palabra clave:	Malaltia de Parkinson Codi genètic Parkinson's disease Genetic code

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oai_identifier_str	oai:recercat.cat:2445/215720
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 Malaltia de Parkinson Codi genètic Parkinson's disease Genetic code
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 Paul, Jefri J Curado, Filipa Skobalj, Snezana Gaber, Hanaa Olmedillas, Maria Morgan, John C Mullin, Stephen Dos Santos Ghilardi, Maria Gabriela Pulera, Mark Musacchio, Thomas Myers, Bennett Negrotti, Anna Pal, Gian Pavese, Nicola Raw, Jason Balck, Alexander Reetz, Kathrin Reiner, Johnathan Lohmann, Katja Stathis, Pantelis Rosenberg, David Ruiz-Lopez, Marta Bogdanovic, Xenia Tönges, Lars Ruiz Martinez, Javier Sammler, Esther Hanssen, Henrike Santos-Lobato, Bruno Lopes Saunders-Pullman, Rachel Schlesinger, Ilana Schofield, Christine M Stocchi, Fabrizio Kasten, Meike Schumacher-Schuh, Artur F Scott, Burton Sesar Ignacio, Ángel Shafer, Stuart J Pinto De Souza, Carolina Toschi, Giulia Ameziane, Najim Sheridan, Ray Silverdale, Monty Tagliati, Michele Tai, Yen F Tumas, Vitor Urban, Peter Paul Vacca, Laura Crosiers, David Afshari, Mitra Vandenberghe, Wim Valente, Enza Maria Djaldetti, Ruth Brüggemann, Norbert Valzania, Franco Vela-Desojo, Lydia Weill, Caroline Aasly, Jan Olav Weise, David Wojcieszek, Joanne Borsche, Max Cullufi, Paskal Wolz, Martin Yahalom, Gilad Yalcin-Cakmakli, Gul Zittel, Simone Rolfs, Arndt Dogu, Okan Zlotnik, Yair Kandaswamy, Krishna K Lange, Lara M Csoti, Ilona Klein, Christine Bauer, Peter Agarwal, Pinky Hassin-Baer, Sharon Aldred, Jason Alonso-Frech, Fernando Hu, Michele T Dashtipour, Khashayar Anderson, Roderick Araújo, Rui Arkadir, David Eggers, Carsten Avenali, Micol Balal, Mehmet Hauser, Robert A Benizri, Sandra Bette, Sagari Bhatia, Perminder Bonello, Michael Demirkiran, Meltem Hummelgen, Eduardo Braga-Neto, Pedro Brauneis, Sarah Cardoso, Francisco Eduardo Costa Cavallieri, Francesco Schell, Nathalie Elibol, Bulent Classen, Joseph Cohen, Lisa Coletta, Della De Carvalho Aguiar, Patricia De Rosa, Anna Ellenbogen, Aaron Ertan, Sibel Fabiani, Giorgio Nieves, Anette Hernández-Vara, Jorge Falkenburger, Björn H Farrow, Simon Percesepe, Antonio Hussey, Kelly Fay-Karmon, Tsviya Ferencz, Gerald J Fonoff, Erich Talamoni Fragoso, Yara Dadalti Genç, Gençer Gorospe, Arantza Herting, Birgit Nitsan, Zeev Grandas, Francisco Gruber, Doreen Gudesblatt, Mark Gurevich, Tanya Infante, Jon Piccoli, Tommaso Hagenah, Johann Hanagasi, Hasmet A Hinson, Vanessa K Hogg, Elliot Isaacson, Stuart H Jaumà, Serge Koleva-Alazeh, Natalia Sophia, Rani Kuhlenbäumer, Gregor Kühn, Andrea Terwecoren, Annelies Oskooilar, Nader Litvan, Irene López-Manzanares, Lydia Luxmore, Mckenzie Prell, Tino Manandhar, Sujeena Marcaud, Veronique Spitz, Mariana Markopoulou, Katerina Marras, Connie Mckenzie, Mark Matarazzo, Michele Öztop-Çakmak, Özgür Thonke, Sven Merello, Marcelo Mollenhauer, Brit
author	Westenberger, Ana
author_facet	Westenberger, Ana Skrahina, Volha Usnich, Tatiana Beetz, Christian Vollstedt, Eva-Juliane Laabs, Björn-Hergen Paul, Jefri J Curado, Filipa Skobalj, Snezana Gaber, Hanaa Olmedillas, Maria Morgan, John C Mullin, Stephen Dos Santos Ghilardi, Maria Gabriela Pulera, Mark Musacchio, Thomas Myers, Bennett Negrotti, Anna Pal, Gian Pavese, Nicola Raw, Jason Balck, Alexander Reetz, Kathrin Reiner, Johnathan Lohmann, Katja Stathis, Pantelis Rosenberg, David Ruiz-Lopez, Marta Bogdanovic, Xenia Tönges, Lars Ruiz Martinez, Javier Sammler, Esther Hanssen, Henrike Santos-Lobato, Bruno Lopes Saunders-Pullman, Rachel Schlesinger, Ilana Schofield, Christine M Stocchi, Fabrizio Kasten, Meike Schumacher-Schuh, Artur F Scott, Burton Sesar Ignacio, Ángel Shafer, Stuart J Pinto De Souza, Carolina Toschi, Giulia Ameziane, Najim Sheridan, Ray Silverdale, Monty Tagliati, Michele Tai, Yen F Tumas, Vitor Urban, Peter Paul Vacca, Laura Crosiers, David Afshari, Mitra Vandenberghe, Wim Valente, Enza Maria Djaldetti, Ruth Brüggemann, Norbert Valzania, Franco Vela-Desojo, Lydia Weill, Caroline Aasly, Jan Olav Weise, David Wojcieszek, Joanne Borsche, Max Cullufi, Paskal Wolz, Martin Yahalom, Gilad Yalcin-Cakmakli, Gul Zittel, Simone Rolfs, Arndt Dogu, Okan Zlotnik, Yair Kandaswamy, Krishna K Lange, Lara M Csoti, Ilona Klein, Christine Bauer, Peter Agarwal, Pinky Hassin-Baer, Sharon Aldred, Jason Alonso-Frech, Fernando Hu, Michele T Dashtipour, Khashayar Anderson, Roderick Araújo, Rui Arkadir, David Eggers, Carsten Avenali, Micol Balal, Mehmet Hauser, Robert A Benizri, Sandra Bette, Sagari Bhatia, Perminder Bonello, Michael Demirkiran, Meltem Hummelgen, Eduardo Braga-Neto, Pedro Brauneis, Sarah Cardoso, Francisco Eduardo Costa Cavallieri, Francesco Schell, Nathalie Elibol, Bulent Classen, Joseph Cohen, Lisa Coletta, Della De Carvalho Aguiar, Patricia De Rosa, Anna Ellenbogen, Aaron Ertan, Sibel Fabiani, Giorgio Nieves, Anette Hernández-Vara, Jorge Falkenburger, Björn H Farrow, Simon Percesepe, Antonio Hussey, Kelly Fay-Karmon, Tsviya Ferencz, Gerald J Fonoff, Erich Talamoni Fragoso, Yara Dadalti Genç, Gençer Gorospe, Arantza Herting, Birgit Nitsan, Zeev Grandas, Francisco Gruber, Doreen Gudesblatt, Mark Gurevich, Tanya Infante, Jon Piccoli, Tommaso Hagenah, Johann Hanagasi, Hasmet A Hinson, Vanessa K Hogg, Elliot Isaacson, Stuart H Jaumà, Serge Koleva-Alazeh, Natalia Sophia, Rani Kuhlenbäumer, Gregor Kühn, Andrea Terwecoren, Annelies Oskooilar, Nader Litvan, Irene López-Manzanares, Lydia Luxmore, Mckenzie Prell, Tino Manandhar, Sujeena Marcaud, Veronique Spitz, Mariana Markopoulou, Katerina Marras, Connie Mckenzie, Mark Matarazzo, Michele Öztop-Çakmak, Özgür Thonke, Sven Merello, Marcelo Mollenhauer, Brit
author_role	author
author2	Skrahina, Volha Usnich, Tatiana Beetz, Christian Vollstedt, Eva-Juliane Laabs, Björn-Hergen Paul, Jefri J Curado, Filipa Skobalj, Snezana Gaber, Hanaa Olmedillas, Maria Morgan, John C Mullin, Stephen Dos Santos Ghilardi, Maria Gabriela Pulera, Mark Musacchio, Thomas Myers, Bennett Negrotti, Anna Pal, Gian Pavese, Nicola Raw, Jason Balck, Alexander Reetz, Kathrin Reiner, Johnathan Lohmann, Katja Stathis, Pantelis Rosenberg, David Ruiz-Lopez, Marta Bogdanovic, Xenia Tönges, Lars Ruiz Martinez, Javier Sammler, Esther Hanssen, Henrike Santos-Lobato, Bruno Lopes Saunders-Pullman, Rachel Schlesinger, Ilana Schofield, Christine M Stocchi, Fabrizio Kasten, Meike Schumacher-Schuh, Artur F Scott, Burton Sesar Ignacio, Ángel Shafer, Stuart J Pinto De Souza, Carolina Toschi, Giulia Ameziane, Najim Sheridan, Ray Silverdale, Monty Tagliati, Michele Tai, Yen F Tumas, Vitor Urban, Peter Paul Vacca, Laura Crosiers, David Afshari, Mitra Vandenberghe, Wim Valente, Enza Maria Djaldetti, Ruth Brüggemann, Norbert Valzania, Franco Vela-Desojo, Lydia Weill, Caroline Aasly, Jan Olav Weise, David Wojcieszek, Joanne Borsche, Max Cullufi, Paskal Wolz, Martin Yahalom, Gilad Yalcin-Cakmakli, Gul Zittel, Simone Rolfs, Arndt Dogu, Okan Zlotnik, Yair Kandaswamy, Krishna K Lange, Lara M Csoti, Ilona Klein, Christine Bauer, Peter Agarwal, Pinky Hassin-Baer, Sharon Aldred, Jason Alonso-Frech, Fernando Hu, Michele T Dashtipour, Khashayar Anderson, Roderick Araújo, Rui Arkadir, David Eggers, Carsten Avenali, Micol Balal, Mehmet Hauser, Robert A Benizri, Sandra Bette, Sagari Bhatia, Perminder Bonello, Michael Demirkiran, Meltem Hummelgen, Eduardo Braga-Neto, Pedro Brauneis, Sarah Cardoso, Francisco Eduardo Costa Cavallieri, Francesco Schell, Nathalie Elibol, Bulent Classen, Joseph Cohen, Lisa Coletta, Della De Carvalho Aguiar, Patricia De Rosa, Anna Ellenbogen, Aaron Ertan, Sibel Fabiani, Giorgio Nieves, Anette Hernández-Vara, Jorge Falkenburger, Björn H Farrow, Simon Percesepe, Antonio Hussey, Kelly Fay-Karmon, Tsviya Ferencz, Gerald J Fonoff, Erich Talamoni Fragoso, Yara Dadalti Genç, Gençer Gorospe, Arantza Herting, Birgit Nitsan, Zeev Grandas, Francisco Gruber, Doreen Gudesblatt, Mark Gurevich, Tanya Infante, Jon Piccoli, Tommaso Hagenah, Johann Hanagasi, Hasmet A Hinson, Vanessa K Hogg, Elliot Isaacson, Stuart H Jaumà, Serge Koleva-Alazeh, Natalia Sophia, Rani Kuhlenbäumer, Gregor Kühn, Andrea Terwecoren, Annelies Oskooilar, Nader Litvan, Irene López-Manzanares, Lydia Luxmore, Mckenzie Prell, Tino Manandhar, Sujeena Marcaud, Veronique Spitz, Mariana Markopoulou, Katerina Marras, Connie Mckenzie, Mark Matarazzo, Michele Öztop-Çakmak, Özgür Thonke, Sven Merello, Marcelo Mollenhauer, Brit
author2_role	author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	Malaltia de Parkinson Codi genètic Parkinson's disease Genetic code
topic	Malaltia de Parkinson Codi genètic Parkinson's disease Genetic code
description	Estimates 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 (similar to 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 x 10(-34)). The probability of a positive PDGT decreased by 3% with every additional AAO year (P = 1 x 10(-35)). Female patients were 22% more likely to have a positive PDGT (P = 3 x 10(-4)), and for individuals with FH+ this likelihood was 55% higher (P = 1 x 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 similar to 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.
publishDate	2024
dc.date.none.fl_str_mv	2024 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/2445/215720
url	https://hdl.handle.net/2445/215720
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	Reproducció del document publicat a: https://doi.org/10.1093/brain/awae188 Brain, 2024, vol. 147, num. 8, p. 2652-2667 https://doi.org/10.1093/brain/awae188
dc.rights.none.fl_str_mv	cc by (c) Westenberger, Ana et al., 2024 http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess
rights_invalid_str_mv	cc by (c) Westenberger, Ana et al., 2024 http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	16 p. application/pdf
dc.publisher.none.fl_str_mv	Oxford University Press (OUP)
publisher.none.fl_str_mv	Oxford University Press (OUP)
dc.source.none.fl_str_mv	Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) 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
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spelling	Relevance of genetic testing in the gene-targeted trial era: the Rostock Parkinson’s disease studyWestenberger, AnaSkrahina, VolhaUsnich, TatianaBeetz, ChristianVollstedt, Eva-JulianeLaabs, Björn-HergenPaul, Jefri JCurado, FilipaSkobalj, SnezanaGaber, HanaaOlmedillas, MariaMorgan, John CMullin, StephenDos Santos Ghilardi, Maria GabrielaPulera, MarkMusacchio, ThomasMyers, BennettNegrotti, AnnaPal, GianPavese, NicolaRaw, JasonBalck, AlexanderReetz, KathrinReiner, JohnathanLohmann, KatjaStathis, PantelisRosenberg, DavidRuiz-Lopez, MartaBogdanovic, XeniaTönges, LarsRuiz Martinez, JavierSammler, EstherHanssen, HenrikeSantos-Lobato, Bruno LopesSaunders-Pullman, RachelSchlesinger, IlanaSchofield, Christine MStocchi, FabrizioKasten, MeikeSchumacher-Schuh, Artur FScott, BurtonSesar Ignacio, ÁngelShafer, Stuart JPinto De Souza, CarolinaToschi, GiuliaAmeziane, NajimSheridan, RaySilverdale, MontyTagliati, MicheleTai, Yen FTumas, VitorUrban, Peter PaulVacca, LauraCrosiers, DavidAfshari, MitraVandenberghe, WimValente, Enza MariaDjaldetti, RuthBrüggemann, NorbertValzania, FrancoVela-Desojo, LydiaWeill, CarolineAasly, Jan OlavWeise, DavidWojcieszek, JoanneBorsche, MaxCullufi, PaskalWolz, MartinYahalom, GiladYalcin-Cakmakli, GulZittel, SimoneRolfs, ArndtDogu, OkanZlotnik, YairKandaswamy, Krishna KLange, Lara MCsoti, IlonaKlein, ChristineBauer, PeterAgarwal, PinkyHassin-Baer, SharonAldred, JasonAlonso-Frech, FernandoHu, Michele TDashtipour, KhashayarAnderson, RoderickAraújo, RuiArkadir, DavidEggers, CarstenAvenali, MicolBalal, MehmetHauser, Robert ABenizri, SandraBette, SagariBhatia, PerminderBonello, MichaelDemirkiran, MeltemHummelgen, EduardoBraga-Neto, PedroBrauneis, SarahCardoso, Francisco Eduardo CostaCavallieri, FrancescoSchell, NathalieElibol, BulentClassen, JosephCohen, LisaColetta, DellaDe Carvalho Aguiar, PatriciaDe Rosa, AnnaEllenbogen, AaronErtan, SibelFabiani, GiorgioNieves, AnetteHernández-Vara, JorgeFalkenburger, Björn HFarrow, SimonPercesepe, AntonioHussey, KellyFay-Karmon, TsviyaFerencz, Gerald JFonoff, Erich TalamoniFragoso, Yara DadaltiGenç, GençerGorospe, ArantzaHerting, BirgitNitsan, ZeevGrandas, FranciscoGruber, DoreenGudesblatt, MarkGurevich, TanyaInfante, JonPiccoli, TommasoHagenah, JohannHanagasi, Hasmet AHinson, Vanessa KHogg, ElliotIsaacson, Stuart HJaumà, SergeKoleva-Alazeh, NataliaSophia, RaniKuhlenbäumer, GregorKühn, AndreaTerwecoren, AnneliesOskooilar, NaderLitvan, IreneLópez-Manzanares, LydiaLuxmore, MckenziePrell, TinoManandhar, SujeenaMarcaud, VeroniqueSpitz, MarianaMarkopoulou, KaterinaMarras, ConnieMckenzie, MarkMatarazzo, MicheleÖztop-Çakmak, ÖzgürThonke, SvenMerello, MarceloMollenhauer, BritMalaltia de ParkinsonCodi genèticParkinson's diseaseGenetic codeEstimates 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 (similar to 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 x 10(-34)). The probability of a positive PDGT decreased by 3% with every additional AAO year (P = 1 x 10(-35)). Female patients were 22% more likely to have a positive PDGT (P = 3 x 10(-4)), and for individuals with FH+ this likelihood was 55% higher (P = 1 x 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 similar to 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.Oxford University Press (OUP)2024202420242024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion16 p.application/pdfhttps://hdl.handle.net/2445/215720Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1093/brain/awae188Brain, 2024, vol. 147, num. 8, p. 2652-2667https://doi.org/10.1093/brain/awae188cc by (c) Westenberger, Ana et al., 2024http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2157202026-05-29T05:05:01Z
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Relevance of genetic testing in the gene-targeted trial era: the Rostock Parkinson’s disease study

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