Author: "Periñán, María Teresa" - Searchworks@Jio Institute Digital Library Search Results

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106 results on '"Periñán, María Teresa"'

1. RAB32 Ser71Arg in autosomal dominant Parkinson's disease: linkage, association, and functional analyses

Author: Gustavsson, Emil K, Follett, Jordan, Trinh, Joanne, Barodia, Sandeep K, Real, Raquel, Liu, Zhiyong, Grant-Peters, Melissa, Fox, Jesse D, Appel-Cresswell, Silke, Stoessl, A Jon, Rajput, Alex, Rajput, Ali H, Auer, Roland, Tilney, Russel, Sturm, Marc, Haack, Tobias B, Lesage, Suzanne, Tesson, Christelle, Brice, Alexis, Vilariño-Güell, Carles, Ryten, Mina, Goldberg, Matthew S, West, Andrew B, Hu, Michele T, Morris, Huw R, Sharma, Manu, Gan-Or, Ziv, Samanci, Bedia, Lis, Pawel, Periñan, Maria Teresa, Amouri, Rim, Ben Sassi, Samia, Hentati, Faycel, Tonelli, Francesca, Alessi, Dario R, and Farrer, Matthew J
Published: 2024
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2. Author Correction: Peripheral inflammatory immune response differs among sporadic and familial Parkinson’s disease

Author: Muñoz-Delgado, Laura, Macías-García, Daniel, Periñán, María Teresa, Jesús, Silvia, Adarmes-Gómez, Astrid D., Bonilla Toribio, Marta, Buiza Rueda, Dolores, Jiménez-Jaraba, María del Valle, Benítez Zamora, Belén, Díaz Belloso, Rafael, García-Díaz, Sergio, Martín-Bórnez, Miguel, Pineda Sánchez, Rocío, Carrillo, Fátima, Gómez-Garre, Pilar, and Mir, Pablo
Published: 2023
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3. Author Correction: The IPDGC/GP2 Hackathon - an open science event for training in data science, genomics, and collaboration using Parkinson’s disease data

Author: Leonard, Hampton L., Murtadha, Ruqaya, Martinez-Carrasco, Alejandro, Jama, Alina, Müller-Nedebock, Amica Corda, Gil-Martinez, Ana-Luisa, Illarionova, Anastasia, Moore, Anni, Bustos, Bernabe I., Jadhav, Bharati, Huxford, Brook, Storm, Catherine, Towns, Clodagh, Vitale, Dan, Chetty, Devina, Yu, Eric, Grenn, Francis P., Salazar, Gabriela, Rateau, Geoffrey, Iwaki, Hirotaka, Elsayed, Inas, Foote, Isabelle Francesca, Jansen van Rensburg, Zuné, Kim, Jonggeol Jeff, Yuan, Jie, Lake, Julie, Brolin, Kajsa, Senkevich, Konstantin, Wu, Lesley, Tan, Manuela M. X., Periñán, María Teresa, Makarious, Mary B., Ta, Michael, Pillay, Nikita Simone, Betancor, Oswaldo Lorenzo, Reyes-Pérez, Paula R., Alvarez Jerez, Pilar, Saini, Prabhjyot, al-Ouran, Rami, Sivakumar, Ramiya, Real, Raquel, Reynolds, Regina H., Hu, Ruifneg, Abrahams, Shameemah, Rao, Shilpa C., Antar, Tarek, Leal, Thiago Peixoto, Iankova, Vassilena, Scotton, William J., Song, Yeajin, Singleton, Andrew, Nalls, Mike A., Dey, Sumit, Bandres-Ciga, Sara, Blauwendraat, Cornelis, and Noyce, Alastair J.
Published: 2023
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4. The IPDGC/GP2 Hackathon - an open science event for training in data science, genomics, and collaboration using Parkinson’s disease data

Author: Leonard, Hampton L., Murtadha, Ruqaya, Martinez-Carrasco, Alejandro, Jama, Alina, Müller-Nedebock, Amica Corda, Gil-Martinez, Ana-Luisa, Illarionova, Anastasia, Moore, Anni, Bustos, Bernabe I., Jadhav, Bharati, Huxford, Brook, Storm, Catherine, Towns, Clodagh, Vitale, Dan, Chetty, Devina, Yu, Eric, Grenn, Francis P., Salazar, Gabriela, Rateau, Geoffrey, Iwaki, Hirotaka, Elsayed, Inas, Foote, Isabelle Francesca, Jansen van Rensburg, Zuné, Kim, Jonggeol Jeff, Yuan, Jie, Lake, Julie, Brolin, Kajsa, Senkevich, Konstantin, Wu, Lesley, Tan, Manuela M. X., Periñán, María Teresa, Makarious, Mary B., Ta, Michael, Pillay, Nikita Simone, Betancor, Oswaldo Lorenzo, Reyes-Pérez, Paula R., Alvarez Jerez, Pilar, Saini, Prabhjyot, al-Ouran, Rami, Sivakumar, Ramiya, Real, Raquel, Reynolds, Regina H., Hu, Ruifneg, Abrahams, Shameemah, Rao, Shilpa C., Antar, Tarek, Leal, Thiago Peixoto, Iankova, Vassilena, Scotton, William J., Song, Yeajin, Singleton, Andrew, Nalls, Mike A., Dey, Sumit, Bandres-Ciga, Sara, Blauwendraat, Cornelis, and Noyce, Alastair J.
Published: 2023
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5. Peripheral inflammatory immune response differs among sporadic and familial Parkinson’s disease

Author: Muñoz-Delgado, Laura, Macías-García, Daniel, Periñán, María Teresa, Jesús, Silvia, Adarmes-Gómez, Astrid D., Bonilla Toribio, Marta, Buiza Rueda, Dolores, Jiménez-Jaraba, María del Valle, Benítez Zamora, Belén, Díaz Belloso, Rafael, García-Díaz, Sergio, Martín-Bórnez, Miguel, Pineda Sánchez, Rocío, Carrillo, Fátima, Gómez-Garre, Pilar, and Mir, Pablo
Published: 2023
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6. Homocysteine levels, genetic background, and cognitive impairment in Parkinson’s disease

Author: Periñán, María Teresa, Macías-García, Daniel, Jesús, Silvia, Martín-Rodríguez, Juan Francisco, Muñoz-Delgado, Laura, Jimenez-Jaraba, Maria Valle, Buiza-Rueda, Dolores, Bonilla-Toribio, Marta, Adarmes-Gómez, Astrid Daniela, Gómez-Garre, Pilar, and Mir, Pablo
Published: 2023
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7. Early downregulation of hsa-miR-144-3p in serum from drug-naïve Parkinson’s disease patients

Author: Zago, Elisa, Dal Molin, Alessandra, Dimitri, Giovanna Maria, Xumerle, Luciano, Pirazzini, Chiara, Bacalini, Maria Giulia, Maturo, Maria Giovanna, Azevedo, Tiago, Spasov, Simeon, Gómez-Garre, Pilar, Periñán, María Teresa, Jesús, Silvia, Baldelli, Luca, Sambati, Luisa, Calandra-Buonaura, Giovanna, Garagnani, Paolo, Provini, Federica, Cortelli, Pietro, Mir, Pablo, Trenkwalder, Claudia, Mollenhauer, Brit, Franceschi, Claudio, Liò, Pietro, and Nardini, Christine
Published: 2022
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8. Transcriptomic analysis reveals an association of FCGBP with Parkinson’s disease

Author: Gómez-Garre, Pilar, Periñán, María Teresa, Jesús, Silvia, Bacalini, Maria Giulia, Garagnani, Paolo, Mollenhauer, Brit, Pirazzini, Chiara, Provini, Federica, Trenkwalder, Claudia, Franceschi, Claudio, and Mir, Pablo
Published: 2022
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9. Smoking is associated with age at disease onset in Parkinson's disease

Author: Adarmes-Gómez, Astrid D., Aguilar, Miquel, Alvarez, Ignacio, Barrero, Francisco Javier, Bergareche Yarza, Jesús Alberto, Bonilla-Toribio, Marta, Botía, Juan A., Boungiorno, María Teresa, Buiza-Rueda, Dolores, Cámara, Ana, Carrillo, Fátima, Cerdan, Debora, Clarimón, Jordi, Compta, Yaroslau, Diez-Fairen, Monica, Dols-Icardo, Oriol, de Fabregues, Oriol, Cartagena, Pilar Sanz, Duarte, Jacinto, Duran, Raquel, Escamilla-Sevilla, Francisco, Ezquerra, Mario, Feliz, Cici, Fernández-Santiago, Rubén, Fernández, Manel, García-Ruiz, Pedro, Gómez-Garre, Pilar, Gomez Heredia, Maria Jose, Gonzalez-Aramburu, Isabel, Gorostidi, Ana, Hoenicka, Janet, Infante, Jon, Jesús, Silvia, Jimenez-Escrig, Adriano, Kulisevsky, Jaime, Labrador-Espinosa, Miguel A., Lopez-Sendon, Jose Luis, López de Munain, Adolfo, Macias-Garcia, Daniel, Martínez-Torres, Irene, Marín, Juan, Marti, Maria Jose, Martínez-Castrillo, Juan Carlos, Álvarez-Santullano, Marina Mata, Mínguez-Castellanos, Adolfo, Mir, Pablo, Rezola, Elisabet Mondragon, Muñoz, Esteban, Pagonabarraga, Javier, Pastor, Pau, Errazquin, Francisco Perez, Periñán, Maria Teresa, Ruiz-Martínez, Javier, Ruz, Clara, Rodriguez, Antonio Sanchez, Sierra, María, Tabernero, Cesar, Tartari, Juan Pablo, Tolosa, Eduard, Valldeoriola, Francesc, Vela, Lydia, Vives, Francisco, Pascual-Sedano, Berta, Hernández-Vara, Jorge, Rolán, Dolores Vilas, Bandrés-Ciga, Sara, Rosas, Irene, Morís, Germán, Coto, Eliecer, Blázquez-Estrada, Marta, Suárez, Esther, García-Fernández, Ciara, Martínez, Carmen, Herrera, Israel Duarte, Pérez-Oliveira, Sergio, Álvarez, Victoria, and Menéndez-González, Manuel
Published: 2022
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10. Role of ATP10B in Parkinson Disease in a cohort from southern Spain

Author: Díaz Belloso, Rafael, primary, Muñoz-Delgado, Laura, additional, Martín-Bornez, Miguel, additional, Ojeda, Elena, additional, Periñán, María Teresa, additional, García-Díaz, Sergio, additional, Bonilla-Toribio, Marta, additional, Buiza-Rueda, Dolores, additional, Pineda Sánchez, Rocío, additional, Jesús, Silvia, additional, Macías-García, Daniel, additional, Adarmes-Gómez, Astrid, additional, Carrillo, Fátima, additional, Mir, Pablo, additional, and Gómez-Garre, Pilar, additional
Published: 2024
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11. AccessPD as a next generation registry to accelerate Parkinson's disease research

Author: Noyce, Alastair J. [0000-0003-3027-5497], Chang, Yun-Hsuan, Periñán, María Teresa, Wilson, Matt, Noyce, Alastair J., Noyce, Alastair J. [0000-0003-3027-5497], Chang, Yun-Hsuan, Periñán, María Teresa, Wilson, Matt, and Noyce, Alastair J.
Abstract: Recruitment is a major rate-limiting factor in Parkinson's disease (PD) research. AccessPD is a unique platform that aims to create a registry of more than 2000 PD patients and a rich database of PD-relevant information. Potential participants are identified using electronic health records (EHRs) in primary care. They are contacted via text message with an individualized link to the study portal. Electronic patient-reported outcomes (ePRO) are collected via online questionnaires and integrated with existing EHR. 200 participants were recruited within the first 6 months, of which 191 answered the follow-up questionnaire. Here, to showcase the potential of AccessPD, we described the most common diagnoses before and after PD diagnosis, the most commonly prescribed drugs, and identified participants who could benefit from device-aided therapies using consensus criteria. AccessPD shows its unique ability to link different data sources for patient stratification in longitudinal studies and recruitment into clinical trials.
Published: 2024

12. Serum lipid profile among sporadic and familial forms of Parkinson’s disease

Author: Macías-García, Daniel, Periñán, María Teresa, Muñoz-Delgado, Laura, Jimenez-Jaraba, María Valle, Labrador-Espinosa, Miguel Ángel, Jesús, Silvia, Buiza-Rueda, Dolores, Méndez-Del Barrio, Carlota, Adarmes-Gómez, Astrid, Gómez-Garre, Pilar, and Mir, Pablo
Published: 2021
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13. A genetic analysis of a Spanish population with early onset Parkinson's disease.

Author: Tejera-Parrado Cristina, Mir Pablo, Periñán María Teresa, Vela-Desojo Lydia, Abreu-Rodríguez Irene, Alonso-Cánovas Araceli, Bernal-Bernal Inmaculada, Bonilla-Toribio Marta, Buiza-Rueda Dolores, Catalán-Alonso María José, García-Ramos Rocío, García-Ruiz Pedro José, Huertas-Fernández Ismael, Jesús Silvia, Miguel A-Espinosa Labrador, López-Manzanares Lydia, Martínez-Castrillo Juan Carlos, Ignacio J Posada, Rojo-Sebastián Ana, Ruiz-Huete Cristina, Del Val Javier, and Pilar Gómez-Garre
Subjects: Medicine, Science
Abstract: IntroductionBoth recessive and dominant genetic forms of Parkinson's disease have been described. The aim of this study was to assess the contribution of several genes to the pathophysiology of early onset Parkinson's disease in a cohort from central Spain.Methods/patientsWe analyzed a cohort of 117 unrelated patients with early onset Parkinson's disease using a pipeline, based on a combination of a next-generation sequencing panel of 17 genes previously related with Parkinson's disease and other Parkinsonisms and CNV screening.ResultsTwenty-six patients (22.22%) carried likely pathogenic variants in PARK2, LRRK2, PINK1, or GBA. The gene most frequently mutated was PARK2, and p.Asn52Metfs*29 was the most common variation in this gene. Pathogenic variants were not observed in genes SNCA, FBXO7, PARK7, HTRA2, DNAJC6, PLA2G6, and UCHL1. Co-occurrence of pathogenic variants involving two genes was observed in ATP13A2 and PARK2 genes, as well as LRRK2 and GIGYF2 genes.ConclusionsOur results contribute to the understanding of the genetic architecture associated with early onset Parkinson's disease, showing both PARK2 and LRRK2 play an important role in Spanish Parkinson's disease patients. Rare variants in ATP13A2 and GIGYF2 may contribute to PD risk. However, a large proportion of genetic components remains unknown. This study might contribute to genetic diagnosis and counseling for families with early onset Parkinson's disease.
Published: 2020
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14. Peripheral inflammatory immune response differs among sporadic and familial Parkinson’s disease

Author: Universidad de Sevilla. Departamento de Medicina, Muñoz-Delgado, Laura, Macías-García, Daniel, Periñán, María Teresa, Jesús, Silvia, Adarmes-Gómez, Astrid D., Bonilla Toribio, Marta, García Díaz, Sergio, Mir Rivera, Pablo, Universidad de Sevilla. Departamento de Medicina, Muñoz-Delgado, Laura, Macías-García, Daniel, Periñán, María Teresa, Jesús, Silvia, Adarmes-Gómez, Astrid D., Bonilla Toribio, Marta, García Díaz, Sergio, and Mir Rivera, Pablo
Abstract: Peripheral inflammatory immune responses are thought to play a major role in the pathogenesis of Parkinson’s disease (PD). The neutrophil-to-lymphocyte ratio (NLR), a biomarker of systemic inflammation, has been reported to be higher in patients with PD than in healthy controls (HCs). The present study was aimed at determining if the peripheral inflammatory immune response could be influenced by the genetic background of patients with PD. We included a discovery cohort with 222 patients with PD (132 sporadic PD, 44 LRRK2-associated PD (with p.G2019S and p.R1441G variants), and 46 GBA-associated PD), as well as 299 HCs. Demographic and clinical data were recorded. Leukocytes and their subpopulations, and the NLR were measured in peripheral blood. Multivariate lineal regression and post-hoc tests were applied to determine the differences among the groups. Subsequently, a replication study using the Parkinson’s Progression Markers Initiative cohort was performed which included 401 patients with PD (281 sPD patients, 66 LRRK2-PD patients, 54 GBA-PD patients) and a group of 174 HCs. Patients with sporadic PD and GBA-associated PD showed a significantly lower lymphocyte count, a non-significantly higher neutrophil count and a significantly higher NLR than HCs. The peripheral inflammatory immune response of patients with LRRK2-associated PD did not differ from HCs. Our study supports the involvement of a peripheral inflammatory immune response in the pathophysiology of sPD and GBA-associated PD. However, this inflammatory response was not found in LRRK2-associated PD, probably reflecting different pathogenic inflammatory mechanisms.
Published: 2023

15. The IPDGC/GP2 Hackathon - an open science event for training in data science, genomics, and collaboration using Parkinson's disease data

Author: Michael J. Fox Foundation for Parkinson's Research, Aligning Science Against Parkinson's, National Institutes of Health (US), National Institute on Aging (US), National Institute of Neurological Disorders and Stroke (US), Leonard, Hampton [0000-0003-2390-8110], Illarionova, Anastasia [0000-0002-1711-7155], Moore, Anni [0000-0003-1953-6449], Bustos, Bernabé I. [0000-0003-2679-9503], Huxford, Brook [0000-0002-5908-6983], Storm, Catherine S. [0000-0003-4957-1712], Towns, Clodagh [0000-0001-8418-6241], Yu, Eric [0000-0003-3525-4564], Elsayed, Inas [0000-0003-4646-8218], Lake, Julie [0000-0002-3441-2455], Brolin, Kajsa [0000-0003-4832-922X], Senkevich, Konstantin [0000-0003-3407-5716], Tan, Manuela M. X. [0000-0001-5835-669X], Makarious, Mary B [.0000-0002-7978-1051], Pillay, Nikita Simone [0000-0002-9058-0920], Betancor, Oswaldo Lorenzo [0000-0002-5607-8363], Real, Raquel [0000-0001-8117-742X], Reynolds, Regina H. [0000-0001-6470-7919], Scotton, William J. [0000-0003-0607-3190], Singleton, Andrew [0000-0001-5606-700X], Dey, Sumit [0000-0002-9087-4486], Blauwendraat, Cornelis [0000-0001-9358-8111], Noyce, Alastair [0000-0003-3027-5497], Leonard, Hampton, Murtadha, Ruqaya, Martínez-Carrasco, Alejandro, Jama, Alina, Müller-Nedebock, Amica Corda, Gil-Martínez, Ana Luisa, Illarionova, Anastasia, Moore, Anni, Bustos, Bernabé I., Jadhav, Bharati, Huxford, Brook, Storm, Catherine S., Towns, Clodagh, Vitale, Dan, Chetty, Devina, Yu, Eric, Grenn, Francis P., Salazar, Gabriela, Rateau, Geoffrey, Iwaki, Hirotaka, Elsayed, Inas, Foote, Isabelle Francesca, Jansen van Rensburg, Zuné, Kim, Jonggeol Jeff, Yuan, Jie, Lake, Julie, Brolin, Kajsa, Senkevich, Konstantin, Wu, Lesley, Tan, Manuela M. X., Periñán, María Teresa, Makarious, Mary B., Ta, Michael, Pillay, Nikita Simone, Betancor, Oswaldo Lorenzo, Reyes-Pérez, Paula R., Álvarez Jerez, Pilar, Saini, Prabhjyot, Al-Ouran, Rami, Sivakumar, Ramiya, Real, Raquel, Reynolds, Regina H., Hu, Ruifneg, Abrahams, Shameemah, Rao, Shilpa C., Antar, Tarek, Leal, Thiago Peixoto, Iankova, Vassilena, Scotton, William J., Song, Yeajin, Singleton, Andrew, Nalls, Mike A., Dey, Sumit, Bandres-Ciga, Sara, Blauwendraat, Cornelis, Noyce, Alastair, International Parkinson’s Disease Genomics Consortium, Global Parkinson’s Genetics Program, Michael J. Fox Foundation for Parkinson's Research, Aligning Science Against Parkinson's, National Institutes of Health (US), National Institute on Aging (US), National Institute of Neurological Disorders and Stroke (US), Leonard, Hampton [0000-0003-2390-8110], Illarionova, Anastasia [0000-0002-1711-7155], Moore, Anni [0000-0003-1953-6449], Bustos, Bernabé I. [0000-0003-2679-9503], Huxford, Brook [0000-0002-5908-6983], Storm, Catherine S. [0000-0003-4957-1712], Towns, Clodagh [0000-0001-8418-6241], Yu, Eric [0000-0003-3525-4564], Elsayed, Inas [0000-0003-4646-8218], Lake, Julie [0000-0002-3441-2455], Brolin, Kajsa [0000-0003-4832-922X], Senkevich, Konstantin [0000-0003-3407-5716], Tan, Manuela M. X. [0000-0001-5835-669X], Makarious, Mary B [.0000-0002-7978-1051], Pillay, Nikita Simone [0000-0002-9058-0920], Betancor, Oswaldo Lorenzo [0000-0002-5607-8363], Real, Raquel [0000-0001-8117-742X], Reynolds, Regina H. [0000-0001-6470-7919], Scotton, William J. [0000-0003-0607-3190], Singleton, Andrew [0000-0001-5606-700X], Dey, Sumit [0000-0002-9087-4486], Blauwendraat, Cornelis [0000-0001-9358-8111], Noyce, Alastair [0000-0003-3027-5497], Leonard, Hampton, Murtadha, Ruqaya, Martínez-Carrasco, Alejandro, Jama, Alina, Müller-Nedebock, Amica Corda, Gil-Martínez, Ana Luisa, Illarionova, Anastasia, Moore, Anni, Bustos, Bernabé I., Jadhav, Bharati, Huxford, Brook, Storm, Catherine S., Towns, Clodagh, Vitale, Dan, Chetty, Devina, Yu, Eric, Grenn, Francis P., Salazar, Gabriela, Rateau, Geoffrey, Iwaki, Hirotaka, Elsayed, Inas, Foote, Isabelle Francesca, Jansen van Rensburg, Zuné, Kim, Jonggeol Jeff, Yuan, Jie, Lake, Julie, Brolin, Kajsa, Senkevich, Konstantin, Wu, Lesley, Tan, Manuela M. X., Periñán, María Teresa, Makarious, Mary B., Ta, Michael, Pillay, Nikita Simone, Betancor, Oswaldo Lorenzo, Reyes-Pérez, Paula R., Álvarez Jerez, Pilar, Saini, Prabhjyot, Al-Ouran, Rami, Sivakumar, Ramiya, Real, Raquel, Reynolds, Regina H., Hu, Ruifneg, Abrahams, Shameemah, Rao, Shilpa C., Antar, Tarek, Leal, Thiago Peixoto, Iankova, Vassilena, Scotton, William J., Song, Yeajin, Singleton, Andrew, Nalls, Mike A., Dey, Sumit, Bandres-Ciga, Sara, Blauwendraat, Cornelis, Noyce, Alastair, International Parkinson’s Disease Genomics Consortium, and Global Parkinson’s Genetics Program
Abstract: Open science and collaboration are necessary to facilitate the advancement of Parkinson's disease (PD) research. Hackathons are collaborative events that bring together people with different skill sets and backgrounds to generate resources and creative solutions to problems. These events can be used as training and networking opportunities, thus we coordinated a virtual 3-day hackathon event, during which 49 early-career scientists from 12 countries built tools and pipelines with a focus on PD. Resources were created with the goal of helping scientists accelerate their own research by having access to the necessary code and tools. Each team was allocated one of nine different projects, each with a different goal. These included developing post-genome-wide association studies (GWAS) analysis pipelines, downstream analysis of genetic variation pipelines, and various visualization tools. Hackathons are a valuable approach to inspire creative thinking, supplement training in data science, and foster collaborative scientific relationships, which are foundational practices for early-career researchers. The resources generated can be used to accelerate research on the genetics of PD.
Published: 2023

16. Cumulative Genetic Score and C9orf72 Repeat Status Independently Contribute to Amyotrophic Lateral Sclerosis Risk in 2 Case-Control Studies

Author: National Amyotrophic Lateral Sclerosis (US), National Institute of Environmental Health Sciences (US), National Institute of Neurological Disorders and Stroke (US), Amyotrophic Lateral Sclerosis Association, Randall W. Whitcomb Fund, University of Michigan, National Institute on Aging (US), National Institutes of Health (US), Comunidad de Madrid, Ministerio de Sanidad (España), Dou, John, Bakulski, Kelly, Guo, Kai, Hur, Junguk, Zhao, Lili, Saez-Atienzar, Sara, Stark, Ali, Chia, Ruth, García-Redondo, Alberto, Rojas-García, Ricardo, Vázquez-Costa, Juan F., Fernández-Santiago, Rubén, Bandres-Ciga, Sara, Gómez-Garre, Pilar, Periñán, María Teresa, Mir, Pablo, Pérez-Tur, Jordi, Cardona, Fernando, Menéndez-González, Manuel, Riancho, Javier, Borrego-Hernández, Daniel, Galán, Lucía, Infante, Jon, Pastor, Pau, Paradas, Carmen, Dols-Icardo, Oriol, Traynor, Bryan J., Feldman, Eva L., Goutman, Stephen A., National Amyotrophic Lateral Sclerosis (US), National Institute of Environmental Health Sciences (US), National Institute of Neurological Disorders and Stroke (US), Amyotrophic Lateral Sclerosis Association, Randall W. Whitcomb Fund, University of Michigan, National Institute on Aging (US), National Institutes of Health (US), Comunidad de Madrid, Ministerio de Sanidad (España), Dou, John, Bakulski, Kelly, Guo, Kai, Hur, Junguk, Zhao, Lili, Saez-Atienzar, Sara, Stark, Ali, Chia, Ruth, García-Redondo, Alberto, Rojas-García, Ricardo, Vázquez-Costa, Juan F., Fernández-Santiago, Rubén, Bandres-Ciga, Sara, Gómez-Garre, Pilar, Periñán, María Teresa, Mir, Pablo, Pérez-Tur, Jordi, Cardona, Fernando, Menéndez-González, Manuel, Riancho, Javier, Borrego-Hernández, Daniel, Galán, Lucía, Infante, Jon, Pastor, Pau, Paradas, Carmen, Dols-Icardo, Oriol, Traynor, Bryan J., Feldman, Eva L., and Goutman, Stephen A.
Abstract: [Background and Objectives] Most patients with amyotrophic lateral sclerosis (ALS) lack a monogenic mutation. This study evaluates ALS cumulative genetic risk in an independent Michigan and Spanish replication cohort using polygenic scores., [Methods] Participant samples from University of Michigan were genotyped and assayed for the chromosome 9 open reading frame 72 hexanucleotide expansion. Final cohort size was 219 ALS and 223 healthy controls after genotyping and participant filtering. Polygenic scores excluding the C9 region were generated using an independent ALS genome-wide association study (20,806 cases, 59,804 controls). Adjusted logistic regression and receiver operating characteristic curves evaluated the association and classification between polygenic scores and ALS status, respectively. Population attributable fractions and pathway analyses were conducted. An independent Spanish study sample (548 cases, 2,756 controls) was used for replication., [Results] Polygenic scores constructed from 275 single-nucleotide variation (SNV) had the best model fit in the Michigan cohort. An SD increase in ALS polygenic score associated with 1.28 (95% CI 1.04–1.57) times higher odds of ALS with area under the curve of 0.663 vs a model without the ALS polygenic score (p value = 1 × 10−6). The population attributable fraction of the highest 20th percentile of ALS polygenic scores, relative to the lowest 80th percentile, was 4.1% of ALS cases. Genes annotated to this polygenic score enriched for important ALS pathomechanisms. Meta-analysis with the Spanish study, using a harmonized 132 single nucleotide variation polygenic score, yielded similar logistic regression findings (odds ratio: 1.13, 95% CI 1.04–1.23)., [Discussion] ALS polygenic scores can account for cumulative genetic risk in populations and reflect disease-relevant pathways. If further validated, this polygenic score will inform future ALS risk models.
Published: 2023

17. PTPA variants and the risk for Parkinson’s disease in diverse ancestry populations

Author: National Institutes of Health (US), National Institute on Aging (US), National Institute of Neurological Disorders and Stroke (US), National Human Genome Research Institute (US), European Commission, Aligning Science Against Parkinson's, Michael J. Fox Foundation for Parkinson's Research, Celgene, Bristol-Myers Squibb, GlaxoSmithKline, Pfizer, Sanofi, Verily Life Sciences, Ostrožovičová, Miriam, Mecheri, Yasser, Al-Mubarak, Bashayer, Al-Tassan, Nada, Makarious, Mary B., Periñán, María Teresa, Bandres-Ciga, Sara, Global Parkinson’s Genetics Program (GP2), National Institutes of Health (US), National Institute on Aging (US), National Institute of Neurological Disorders and Stroke (US), National Human Genome Research Institute (US), European Commission, Aligning Science Against Parkinson's, Michael J. Fox Foundation for Parkinson's Research, Celgene, Bristol-Myers Squibb, GlaxoSmithKline, Pfizer, Sanofi, Verily Life Sciences, Ostrožovičová, Miriam, Mecheri, Yasser, Al-Mubarak, Bashayer, Al-Tassan, Nada, Makarious, Mary B., Periñán, María Teresa, Bandres-Ciga, Sara, and Global Parkinson’s Genetics Program (GP2)
Published: 2023

18. Mendelian Randomisation Confirms the Role of Y-Chromosome Loss in Alzheimer’s Disease Aetiopathogenesis in Men

Author: Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas (España), Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Ace Alzheimer Center Barcelona, Grifols, Fundación la Caixa, European Commission, European Alzheimer's Disease DNA BioBank, García-González, Pablo, Rojas, Itziar de, Moreno-Grau, Sonia, Montrreal, Laura, Puerta, Raquel, Alarcón-Martín, Emilio, Quintela, Inés, Orellana, Adela, Andrade, Victor, Martino-Adami, Pamela V., Heilmann-Heimbach, Stefanie, Gómez-Garre, Pilar, Periñán, María Teresa, Álvarez, Ignacio, Díez-Fairen, Mónica, Nuñez-Llaves, Raul, Olivé-Roig, Claudia, García-Ribas, Guillermo, Menéndez-González, Manuel, Martínez, Carmen, Aguilar Barberá, Miquel, Buongiorno, Maria Teresa, Franco-Macías, Emilio, Sáez, María Eugenia, Cano, Amanda, Bullido, María Jesús, Real, Luis Miguel, Rodríguez-Rodríguez, Eloy, Royo, José Luis, Álvarez, Victoria, Pastor, Pau, Piñol-Ripoll, Gerard, Mir, Pablo, Calero, Miguel, Medina-Padilla, Miguel, Sánchez-Juan, Pascual, Carracedo, Ángel, Valero, Sergi, Hernández, Isabel, Tárraga, Lluís, Ramírez, Alfredo, Boada, Mercè, Ruiz, Agustín, Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas (España), Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Ace Alzheimer Center Barcelona, Grifols, Fundación la Caixa, European Commission, European Alzheimer's Disease DNA BioBank, García-González, Pablo, Rojas, Itziar de, Moreno-Grau, Sonia, Montrreal, Laura, Puerta, Raquel, Alarcón-Martín, Emilio, Quintela, Inés, Orellana, Adela, Andrade, Victor, Martino-Adami, Pamela V., Heilmann-Heimbach, Stefanie, Gómez-Garre, Pilar, Periñán, María Teresa, Álvarez, Ignacio, Díez-Fairen, Mónica, Nuñez-Llaves, Raul, Olivé-Roig, Claudia, García-Ribas, Guillermo, Menéndez-González, Manuel, Martínez, Carmen, Aguilar Barberá, Miquel, Buongiorno, Maria Teresa, Franco-Macías, Emilio, Sáez, María Eugenia, Cano, Amanda, Bullido, María Jesús, Real, Luis Miguel, Rodríguez-Rodríguez, Eloy, Royo, José Luis, Álvarez, Victoria, Pastor, Pau, Piñol-Ripoll, Gerard, Mir, Pablo, Calero, Miguel, Medina-Padilla, Miguel, Sánchez-Juan, Pascual, Carracedo, Ángel, Valero, Sergi, Hernández, Isabel, Tárraga, Lluís, Ramírez, Alfredo, Boada, Mercè, and Ruiz, Agustín
Abstract: Mosaic loss of chromosome Y (mLOY) is a common ageing-related somatic event and has been previously associated with Alzheimer’s disease (AD). However, mLOY estimation from genotype microarray data only reflects the mLOY degree of subjects at the moment of DNA sampling. Therefore, mLOY phenotype associations with AD can be severely age-confounded in the context of genome-wide association studies. Here, we applied Mendelian randomisation to construct an age-independent mLOY polygenic risk score (mloy-PRS) using 114 autosomal variants. The mloy-PRS instrument was associated with an 80% increase in mLOY risk per standard deviation unit (p = 4.22 × 10−20) and was orthogonal with age. We found that a higher genetic risk for mLOY was associated with faster progression to AD in men with mild cognitive impairment (hazard ratio (HR) = 1.23, p = 0.01). Importantly, mloy-PRS had no effect on AD conversion or risk in the female group, suggesting that these associations are caused by the inherent loss of the Y chromosome. Additionally, the blood mLOY phenotype in men was associated with increased cerebrospinal fluid levels of total tau and phosphorylated tau181 in subjects with mild cognitive impairment and dementia. Our results strongly suggest that mLOY is involved in AD pathogenesis.
Published: 2023

19. Peripheral inflammatory immune response differs among sporadic and familial Parkinson’s disease

Author: Instituto de Salud Carlos III, Hospital Universitario Virgen del Rocío, CSIC-JA-USE - Instituto de Biomedicina de Sevilla (IBIS), European Commission, Junta de Andalucía, Ministerio de Educación (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Ministerio de Economía y Competitividad (España), Muñoz-Delgado, Laura, Macías García, Daniel, Periñán, María Teresa, Jesús Maestre, Silvia, Adarmes Gómez, A. D., Bonilla-Toribio, Marta, Buiza-Rueda, Dolores, Jiménez-Jaraba, María Valle, Benítez Zamora, Belén, Díaz-Belloso, Rafael, García-Díaz, Sergio, Martín-Bórnez, Miguel, Pineda-Sánchez, Rocío, Carrillo, Fátima, Gómez-Garre, Pilar, Mir, Pablo, Instituto de Salud Carlos III, Hospital Universitario Virgen del Rocío, CSIC-JA-USE - Instituto de Biomedicina de Sevilla (IBIS), European Commission, Junta de Andalucía, Ministerio de Educación (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Ministerio de Economía y Competitividad (España), Muñoz-Delgado, Laura, Macías García, Daniel, Periñán, María Teresa, Jesús Maestre, Silvia, Adarmes Gómez, A. D., Bonilla-Toribio, Marta, Buiza-Rueda, Dolores, Jiménez-Jaraba, María Valle, Benítez Zamora, Belén, Díaz-Belloso, Rafael, García-Díaz, Sergio, Martín-Bórnez, Miguel, Pineda-Sánchez, Rocío, Carrillo, Fátima, Gómez-Garre, Pilar, and Mir, Pablo
Abstract: Peripheral inflammatory immune responses are thought to play a major role in the pathogenesis of Parkinson’s disease (PD). The neutrophil-to-lymphocyte ratio (NLR), a biomarker of systemic inflammation, has been reported to be higher in patients with PD than in healthy controls (HCs). The present study was aimed at determining if the peripheral inflammatory immune response could be influenced by the genetic background of patients with PD. We included a discovery cohort with 222 patients with PD (132 sporadic PD, 44 LRRK2-associated PD (with p.G2019S and p.R1441G variants), and 46 GBA-associated PD), as well as 299 HCs. Demographic and clinical data were recorded. Leukocytes and their subpopulations, and the NLR were measured in peripheral blood. Multivariate lineal regression and post-hoc tests were applied to determine the differences among the groups. Subsequently, a replication study using the Parkinson’s Progression Markers Initiative cohort was performed which included 401 patients with PD (281 sPD patients, 66 LRRK2-PD patients, 54 GBA-PD patients) and a group of 174 HCs. Patients with sporadic PD and GBA-associated PD showed a significantly lower lymphocyte count, a non-significantly higher neutrophil count and a significantly higher NLR than HCs. The peripheral inflammatory immune response of patients with LRRK2-associated PD did not differ from HCs. Our study supports the involvement of a peripheral inflammatory immune response in the pathophysiology of sPD and GBA-associated PD. However, this inflammatory response was not found in LRRK2-associated PD, probably reflecting different pathogenic inflammatory mechanisms.
Published: 2023

20. Homocysteine levels, genetic background, and cognitive impairment in Parkinson’s disease

Author: Conferencia de Rectores de las Universidades Españolas, Consejo Superior de Investigaciones Científicas (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Instituto de Salud Carlos III, European Commission, Junta de Andalucía, Fundación Alicia Koplowitz, Universidad de Sevilla, Periñán, María Teresa, Macías García, Daniel, Jesús Maestre, Silvia, Martín-Rodríguez, Juan Francisco, Muñoz-Delgado, Laura, Jiménez-Jaraba, María Valle, Buiza-Rueda, Dolores, Bonilla-Toribio, Marta, Adarmes Gómez, A. D., Gómez-Garre, Pilar, Mir, Pablo, Conferencia de Rectores de las Universidades Españolas, Consejo Superior de Investigaciones Científicas (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Instituto de Salud Carlos III, European Commission, Junta de Andalucía, Fundación Alicia Koplowitz, Universidad de Sevilla, Periñán, María Teresa, Macías García, Daniel, Jesús Maestre, Silvia, Martín-Rodríguez, Juan Francisco, Muñoz-Delgado, Laura, Jiménez-Jaraba, María Valle, Buiza-Rueda, Dolores, Bonilla-Toribio, Marta, Adarmes Gómez, A. D., Gómez-Garre, Pilar, and Mir, Pablo
Abstract: [Background] Hyperhomocysteinemia is considered an independent risk factor for cognitive impairment., [Objective] To study the correlation between homocysteine levels and cognitive impairment in patients with PD., [Methods] We conducted a case–control study that included 246 patients with PD, of whom 32 were cognitively impaired. The levels of homocysteine, folate, and vitamin B12 were measured in peripheral blood. Multivariate logistic regression analysis was applied to determine differences in homocysteine levels between PD patients with and without cognitive impairment. A meta-analysis was performed to clarify the role of Hcy levels in PD with cognitive decline. Five polymorphisms in genes involved in Hcy metabolism, including MTHFR rs1801133 and rs1801131, COMT rs4680, MTRR rs1801394, and TCN2 rs1801198, were genotyped., [Results] Our case–control study showed that homocysteine levels were associated with cognitive impairment in PD after adjusting for possible confounding factors such as levodopa equivalent daily dose. The results of our meta-analysis further supported the positive association between homocysteine levels and cognition in PD. We found that the MTHFR rs1801133 TT genotype led to higher homocysteine levels in PD patients, whereas the MTHFR rs1801131 CC genotype resulted in higher folate levels. However, the polymorphisms studied were not associated with cognitive impairment in PD., [Conclusions] Increased homocysteine levels were a risk factor for cognitive decline in PD. However, no association was found between polymorphisms in genes involved in homocysteine metabolism and cognitive impairment in PD. Large-scale studies of ethnically diverse populations are required to definitively assess the relationship between MTHFR and cognitive impairment in PD.
Published: 2023

21. Defining the causes of sporadic Parkinson’s disease in the global Parkinson’s genetics program (GP2)

Author: National Institute on Aging (US), National Institutes of Health (US), Aligning Science Against Parkinson's, Parkinson Research Foundation, Department of Health and Human Services (US), Towns, Clodagh, Richer, Madeleine, Jasaityte, Simona, Stafford, Eleanor J., Joubert, Julie, Antar, Tarek, Martínez-Carrasco, Alejandro, Makarious, Mary B., Casey, Bradford, Vitale, Dan, Levine, Kristin, Leonard, Hampton, Pantazis, Caroline B., Screven, Laurel A., Hernández, Dena G., Wegel, Claire E., Solle, Justin, Nalls, Mike A., Blauwendraat, Cornelis, Singleton, Andrew B., Tan, Manuela M. X., Iwaki, Hirotaka, Morris, Huw, Global Parkinson’s Genetics Program (GP2), Periñán, María Teresa, National Institute on Aging (US), National Institutes of Health (US), Aligning Science Against Parkinson's, Parkinson Research Foundation, Department of Health and Human Services (US), Towns, Clodagh, Richer, Madeleine, Jasaityte, Simona, Stafford, Eleanor J., Joubert, Julie, Antar, Tarek, Martínez-Carrasco, Alejandro, Makarious, Mary B., Casey, Bradford, Vitale, Dan, Levine, Kristin, Leonard, Hampton, Pantazis, Caroline B., Screven, Laurel A., Hernández, Dena G., Wegel, Claire E., Solle, Justin, Nalls, Mike A., Blauwendraat, Cornelis, Singleton, Andrew B., Tan, Manuela M. X., Iwaki, Hirotaka, Morris, Huw, Global Parkinson’s Genetics Program (GP2), and Periñán, María Teresa
Abstract: The Global Parkinson’s Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic and clinical data for use in large-scale analyses to dramatically expand our understanding of the genetic architecture of PD. This report details the workflow for cohort integration into the complex arm of GP2, and together with our outline of the monogenic hub in a companion paper, provides a generalizable blueprint for establishing large scale collaborative research consortia.
Published: 2023

22. Mendelian Randomisation Confirms the Role of Y-Chromosome Loss in Alzheimer’s Disease Aetiopathogenesis in Men

Author: García-González, Pablo, primary, de Rojas, Itziar, additional, Moreno-Grau, Sonia, additional, Montrreal, Laura, additional, Puerta, Raquel, additional, Alarcón-Martín, Emilio, additional, Quintela, Inés, additional, Orellana, Adela, additional, Andrade, Victor, additional, Adami, Pamela V. Martino, additional, Heilmann-Heimbach, Stefanie, additional, Gomez-Garre, Pilar, additional, Periñán, María Teresa, additional, Alvarez, Ignacio, additional, Diez-Fairen, Monica, additional, Nuñez Llaves, Raul, additional, Olivé Roig, Claudia, additional, Garcia-Ribas, Guillermo, additional, Menéndez-González, Manuel, additional, Martínez, Carmen, additional, Aguilar, Miquel, additional, Buongiorno, Mariateresa, additional, Franco-Macías, Emilio, additional, Saez, Maria Eugenia, additional, Cano, Amanda, additional, Bullido, Maria J., additional, Real, Luis Miguel, additional, Rodríguez-Rodríguez, Eloy, additional, Royo, Jose Luís, additional, Álvarez, Victoria, additional, Pastor, Pau, additional, Piñol-Ripoll, Gerard, additional, Mir, Pablo, additional, Lara, Miguel Calero, additional, Padilla, Miguel Medina, additional, Sánchez-Juan, Pascual, additional, Carracedo, Angel, additional, Valero, Sergi, additional, Hernandez, Isabel, additional, Tàrraga, Lluis, additional, Ramirez, Alfredo, additional, Boada, Mercé, additional, and Ruiz, Agustín, additional
Published: 2023
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23. The IPDGC/GP2 Hackathon - an open science event for training in data science, genomics, and collaboration using Parkinson's disease data

Author: Leonard, Hampton L, Murtadha, Ruqaya, Huxford, Brook, Storm, Catherine, Towns, Clodagh, Vitale, Dan, Chetty, Devina, Yu, Eric, Grenn, Francis P, Salazar, Gabriela, Rateau, Geoffrey, Iwaki, Hirotaka, Martinez-Carrasco, Alejandro, Elsayed, Inas, Foote, Isabelle Francesca, Jansen van Rensburg, Zuné, Kim, Jonggeol Jeff, Yuan, Jie, Lake, Julie, Brolin, Kajsa, Senkevich, Konstantin, Wu, Lesley, Tan, Manuela M X, Jama, Alina, Periñán, María Teresa, Makarious, Mary B, Ta, Michael, Pillay, Nikita Simone, Betancor, Oswaldo Lorenzo, Reyes-Pérez, Paula R, Alvarez Jerez, Pilar, Saini, Prabhjyot, Al-Ouran, Rami, Sivakumar, Ramiya, Müller-Nedebock, Amica Corda, Real, Raquel, Reynolds, Regina H, Hu, Ruifneg, Abrahams, Shameemah, Rao, Shilpa C, Antar, Tarek, Leal, Thiago Peixoto, Iankova, Vassilena, Scotton, William J, Song, Yeajin, Gil-Martinez, Ana-Luisa, Singleton, Andrew, Nalls, Mike A, Dey, Sumit, Bandres-Ciga, Sara, Blauwendraat, Cornelis, Noyce, Alastair J, Program, The Global Parkinson’s Genetics, Illarionova, Anastasia, Moore, Anni, Bustos, Bernabe I, Jadhav, Bharati, and Consortium, International Parkinson Disease Genomics
Subjects: Cellular and Molecular Neuroscience, Neurology, Neurology (clinical), ddc:610
Abstract: Open science and collaboration are necessary to facilitate the advancement of Parkinson’s disease (PD) research. Hackathons are collaborative events that bring together people with different skill sets and backgrounds to generate resources and creative solutions to problems. These events can be used as training and networking opportunities, thus we coordinated a virtual 3-day hackathon event, during which 49 early-career scientists from 12 countries built tools and pipelines with a focus on PD. Resources were created with the goal of helping scientists accelerate their own research by having access to the necessary code and tools. Each team was allocated one of nine different projects, each with a different goal. These included developing post-genome-wide association studies (GWAS) analysis pipelines, downstream analysis of genetic variation pipelines, and various visualization tools. Hackathons are a valuable approach to inspire creative thinking, supplement training in data science, and foster collaborative scientific relationships, which are foundational practices for early-career researchers. The resources generated can be used to accelerate research on the genetics of PD.
Published: 2023

24. Author Correction: The IPDGC/GP2 Hackathon - an open science event for training in data science, genomics, and collaboration using Parkinson's disease data

Author: Leonard, Hampton L, Murtadha, Ruqaya, Huxford, Brook, Storm, Catherine, Towns, Clodagh, Vitale, Dan, Chetty, Devina, Yu, Eric, Grenn, Francis P, Salazar, Gabriela, Rateau, Geoffrey, Iwaki, Hirotaka, Martinez-Carrasco, Alejandro, Elsayed, Inas, Foote, Isabelle Francesca, Jansen van Rensburg, Zuné, Kim, Jonggeol Jeff, Yuan, Jie, Lake, Julie, Brolin, Kajsa, Senkevich, Konstantin, Wu, Lesley, Tan, Manuela M X, Jama, Alina, Periñán, María Teresa, Makarious, Mary B, Ta, Michael, Pillay, Nikita Simone, Betancor, Oswaldo Lorenzo, Reyes-Pérez, Paula R, Alvarez Jerez, Pilar, Saini, Prabhjyot, Al-Ouran, Rami, Sivakumar, Ramiya, Müller-Nedebock, Amica Corda, Real, Raquel, Reynolds, Regina H, Hu, Ruifneg, Abrahams, Shameemah, Rao, Shilpa C, Antar, Tarek, Leal, Thiago Peixoto, Iankova, Vassilena, Scotton, William J, Song, Yeajin, Gil-Martinez, Ana-Luisa, Singleton, Andrew, Nalls, Mike A, Dey, Sumit, Bandres-Ciga, Sara, Blauwendraat, Cornelis, Noyce, Alastair J, Program, The Global Parkinson’s Genetics, Illarionova, Anastasia, Moore, Anni, Bustos, Bernabe I, Jadhav, Bharati, and Consortium, International Parkinson Disease Genomics
Subjects: ddc:610
Published: 2023

25. Homocysteine levels, genetic background, and cognitive impairment in Parkinson’s disease

Author: Periñán, María Teresa, primary, Macías-García, Daniel, additional, Jesús, Silvia, additional, Martín-Rodríguez, Juan Francisco, additional, Muñoz-Delgado, Laura, additional, Jimenez-Jaraba, Maria Valle, additional, Buiza-Rueda, Dolores, additional, Bonilla-Toribio, Marta, additional, Adarmes-Gómez, Astrid Daniela, additional, Gómez-Garre, Pilar, additional, and Mir, Pablo, additional
Published: 2022
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26. Intermediate and ExpandedHTTAlleles and the Risk for α‐Synucleinopathies

Author: Pérez‐Oliveira, Sergio, primary, Álvarez, Ignacio, additional, Rosas, Irene, additional, Menendez‐González, Manuel, additional, Blázquez‐Estrada, Marta, additional, Aguilar, Miquel, additional, Corte, Daniela, additional, Buongiorno, Mariateresa, additional, Molina‐Porcel, Laura, additional, Aldecoa, Iban, additional, Martí, María J., additional, Sánchez‐Juan, Pascual, additional, Infante, Jon, additional, González‐Aramburu, Isabel, additional, García‐González, Pablo, additional, Rosende‐Roca, Maitée, additional, Boada, Mercè, additional, Ruiz, Agustín, additional, Periñán, María Teresa, additional, Macías‐García, Daniel, additional, Muñoz‐Delgado, Laura, additional, Gómez‐Garre, Pilar, additional, Mir, Pablo, additional, Clarimón, Jordi, additional, Lleo, Alberto, additional, Alcolea, Daniel, additional, De la Casa‐Fages, Beatriz, additional, Duarte, Israel, additional, Álvarez, Victoria, additional, and Pastor, Pau, additional
Published: 2022
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27. Increased Stroke Risk in Patients with Parkinson’s Disease with LRRK2 Mutations

Author: Universidad de Sevilla. Departamento de Medicina, Universidad de Sevilla. CTS630: Trastornos del movimiento., Macías-García, Daniel, Periñán, María Teresa, Muñoz Delgado, Laura, Jesús, Silvia, Jiménez Jaraba, María Valle, Buiza Rueda, Dolores, Bonilla Toribio, Marta, Adarmes-Gómez, Astrid, Carrillo, Fátima, Gómez Garre, Pilar, Mir Rivera, Pablo, Universidad de Sevilla. Departamento de Medicina, Universidad de Sevilla. CTS630: Trastornos del movimiento., Macías-García, Daniel, Periñán, María Teresa, Muñoz Delgado, Laura, Jesús, Silvia, Jiménez Jaraba, María Valle, Buiza Rueda, Dolores, Bonilla Toribio, Marta, Adarmes-Gómez, Astrid, Carrillo, Fátima, Gómez Garre, Pilar, and Mir Rivera, Pablo
Abstract: Parkinson’s disease (PD) is associated with an increasedstroke risk, however, no relationship between coronary arterydisease (CAD) and PD was found.1To date, little is knownabout the influence of PD-related genes, such as the leucine-rich repeat kinase 2 (LRRK2), the parkin (PRKN) and theglucocerebrosidase (GBA) genes, in the vascular risk of thesepatients. This work aims to determine whether the vascularrisk differs between sporadic/familial PD forms and controls.
Published: 2022

28. Transcriptomic analysis reveals an association of FCGBP with Parkinson's disease

Author: European Commission, Instituto de Salud Carlos III, Junta de Andalucía, Gómez-Garre, Pilar [0000-0002-0437-6182], Provini, Federica [0000-0001-9063-2658], Claudio Franceschi [0000-0001-9841-6386], Pablo Mir [0000-0003-1656-302X], Gómez-Garre, Pilar, Periñán, María Teresa, Jesús Maestre, Silvia, Bacalini, Maria Giulia, Garagnani, Paolo, Mollenhauer, Brit, Pirazzini, Chiara, Provini, Federica, Trenkwalder, Claudia, Franceschi, Claudio, Mir, Pablo, European Commission, Instituto de Salud Carlos III, Junta de Andalucía, Gómez-Garre, Pilar [0000-0002-0437-6182], Provini, Federica [0000-0001-9063-2658], Claudio Franceschi [0000-0001-9841-6386], Pablo Mir [0000-0003-1656-302X], Gómez-Garre, Pilar, Periñán, María Teresa, Jesús Maestre, Silvia, Bacalini, Maria Giulia, Garagnani, Paolo, Mollenhauer, Brit, Pirazzini, Chiara, Provini, Federica, Trenkwalder, Claudia, Franceschi, Claudio, and Mir, Pablo
Abstract: Transcriptomics in Parkinson’s disease (PD) offers new insights into the molecular mechanism of PD pathogenesis. Several pathways, such as inflammation and protein degradation, have been identified by differential gene expression analysis. Our aim was to identify gene expression differences underlying the disease etiology and the discovery of pre-symptomatic risk biomarkers for PD from a multicenter study in the context of the PROPAG-AGEING project. We performed RNA sequencing from 47 patients with de novo PD, 10 centenarians, and 65 healthy controls. Using identified differentially expressed genes, functional annotations were assigned using gene ontology to unveil significant enriched biological processes. The expression of 16 selected genes was validated using OpenArray® assays and samples from independent cohorts of 201 patients with advanced PD, 340 healthy siblings of PD patients, and 177 healthy controls. Differential gene expression analysis identified higher FCGBP expression in patients with de novo PD compared with healthy controls and compared with centenarians. Furthermore, FCGBP showed no differences in terms of population origin or aging process. The increased FCGBP expression was validated in patients with advanced PD and their siblings. Thus, we provided evidence for an upregulation of FCGBP mRNA levels not only in patients with PD but also in individuals at putative higher risk of PD, suggesting that it could be important in gut–brain PD interaction, mediating the connection between microbiota and intestinal inflammatory processes, as well as neuroinflammation and neurodegeneration.
Published: 2022

29. Effect Modification between Genes and Environment and Parkinson's Disease Risk

Author: Aligning Science Against Parkinson's, Michael J. Fox Foundation for Parkinson's Research, National Institute on Aging (US), National Institutes of Health (US), Barts Charity, Periñán, María Teresa, Brolin, Kajsa, Bandres-Ciga, Sara, Blauwendraat, Cornelis, Klein, Christine, Gan-Or, Ziv, Singleton, Andrew, Gómez-Garre, Pilar, Swanberg, Maria, Mir, Pablo, Noyce, Alastair, Aligning Science Against Parkinson's, Michael J. Fox Foundation for Parkinson's Research, National Institute on Aging (US), National Institutes of Health (US), Barts Charity, Periñán, María Teresa, Brolin, Kajsa, Bandres-Ciga, Sara, Blauwendraat, Cornelis, Klein, Christine, Gan-Or, Ziv, Singleton, Andrew, Gómez-Garre, Pilar, Swanberg, Maria, Mir, Pablo, and Noyce, Alastair
Abstract: Parkinson's disease (PD) is a complex neurodegenerative condition in which genetic and environmental factors interact to contribute to its etiology. Remarkable progress has been made in deciphering disease etiology through genetic approaches, but there is limited data about how environmental and genetic factors interact to modify penetrance, risk, and disease severity. Here, we provide insights into environmental modifiers of PD, discussing precedents from other neurological and non-neurological conditions. Based on these examples, we outline genetic and environmental factors contributing to PD and review potential environmental modifiers of penetrance and clinical variability in monogenic and idiopathic PD. We also highlight the potential challenges and propose how future studies might tackle these important questions. ANN NEUROL 2022;92:715-724.
Published: 2022

30. The IPDGC/GP2 Hackathon - an open science event for training in data science, genomics, and collaboration using Parkinson’s disease data

Author: Leonard, Hampton L., primary, Murtadha, Ruqaya, additional, Martinez-Carrasco, Alejandro, additional, Muller-Nedebock, Amica, additional, Gil-Martinez, Ana-Luisa, additional, Illarionova, Anastasia, additional, Moore, Anni, additional, Bustos, Bernabe I., additional, Jadhav, Bharati, additional, Huxford, Brook, additional, Storm, Catherine, additional, Towns, Clodagh, additional, Vitale, Dan, additional, Chetty, Devina, additional, Yu, Eric, additional, Jama, Fatumah, additional, Grenn, Francis P., additional, Salazar, Gabriela, additional, Rateau, Geoffrey, additional, Iwaki, Hirotaka, additional, Elsayed, Inas, additional, Foote, Isabelle, additional, van Rensburg, Zuné Jansen, additional, Kim, Jonggeol Jeff, additional, Yuan, Jie, additional, Lake, Julie, additional, Brolin, Kajsa, additional, Senkevich, Konstantin, additional, Wu, Lesley, additional, Tan, Manuela M.X., additional, Periñán, María Teresa, additional, Makarious, Mary B, additional, Ta, Michael, additional, Pillay, Nikita Simone, additional, Betancor, Oswaldo Lorenzo, additional, Reyes-Pérez, Paula R., additional, Jerez, Pilar Alvarez, additional, Saini, Prabhjyot, additional, al-Ouran, Rami, additional, Sivakumar, Ramiya, additional, Real, Raquel, additional, Reynolds, Regina H., additional, Hu, Ruifneg, additional, Abrahams, Shameemah, additional, Rao, Shilpa C., additional, Antar, Tarek, additional, Leal, Thiago Peixoto, additional, Iankova, Vassilena, additional, Scotton, William J., additional, Song, Yeajin, additional, Singleton, Andrew, additional, Nalls, Mike A., additional, Dey, Sumit, additional, Bandres-Ciga, Sara, additional, Blauwendraat, Cornelis, additional, and Noyce, Alastair J., additional
Published: 2022
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31. Reply to: “Increased Stroke Risk in Patients with Parkinson's Disease with LRRK2 Mutations”

Author: Macías‐García, Daniel, primary, Periñán, María Teresa, additional, Muñoz‐Delgado, Laura, additional, Jesús, Silvia, additional, Jimenez‐Jaraba, María Valle, additional, Buiza‐Rueda, Dolores, additional, Bonilla‐Toribio, Marta, additional, Adarmes‐Gómez, Astrid, additional, Carrillo, Fátima, additional, Gómez‐Garre, Pilar, additional, and Mir, Pablo, additional
Published: 2022
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32. Genomic Characterization of Host Factors Related to SARS-CoV-2 Infection in People with Dementia and Control Populations: The GR@ACE/DEGESCO Study

Author: Rojas, Itziar de, Hernández, Isabel, Montrreal, Laura, Quintela, Inés, Calero, Miguel, Royo, José Luis, Huerto Vilas, Raquel, González-Pérez, Antonio, Franco-Macías, Emilio, Macias, Juan, Menéndez-González, Manuel, Frank-García, Ana, Díez-Fairen, Mónica, Lage, Carmen, García-Madrona, Sebastián, Aguilera, Nuria, Garcia-González, Pablo, Puerta, Raquel, Sotolongo-Grau, Oscar, Alonso-Lana, Silvia, Rábano, Alberto, Arias Pastor, Alfonso, Pastor, Ana Belén, Corma-Gómez, Anaïs, Martin Montes, Ángel, Martínez Rodríguez, Carmen, Buiza-Rueda, Dolores, Periñán, María Teresa, Rodríguez-Rodríguez, Eloy, Álvarez, Ignacio, Rosas Allende, Irene, Pineda, Juan A., Bernal Sánchez-Arjona, María, Fernández-Fuertes, Marta, Mendoza, Silvia, Ser, Teodoro del, GR@ACE, DEGESCO Consortium, García-Ribas, Guillermo, Sanchez-Juan, Pascual, Pastor, Pau, Bullido, María Jesús, Álvarez, Victoria, Real, Luis M., Mir, Pablo, Piñol-Ripoll, Gerard, García-Alberca, José María, Medina, Miguel, Orellana, Adelina, Butler, Christopher R., Marquie, Marta, Sáez, María Eugenia, Carracedo, Ángel, Tárraga, Lluís, Boada, Mercè, Ruiz, Agustín, Instituto de Salud Carlos III, Unión Europea, Grifols (Spain), Fundación La Caixa, Fundació ACE, Centro de Investigación Biomédica en Red - CIBERNED (Enfermedades Neurodegenerativas), Fundación Reina Sofía, Grifols, La Caixa, Ace Alzheimer Center Barcelona, Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas (España), European Commission, Rojas, Itziar de [0000-0002-2148-381X], Calero, Miguel [0000-0001-5366-3324], Menéndez-González, Manuel [0000-0002-5218-0774], Díez-Fairen, Mónica [0000-0003-1882-0309], Rábano, Alberto [0000-0001-9320-6566], Rodríguez-Rodríguez, Eloy [0000-0001-7742-677X], Álvarez, Ignacio [0000-0002-8537-3935], Bullido, María Jesús [0000-0002-6477-1117], Álvarez, Victoria [0000-0002-1916-2523], Real, Luis M. [0000-0003-4932-7429], Medina, Miguel [0000-0002-7016-5340], Butler, Christopher R. [0000-0002-7502-9284], Sáez, María Eugenia [0000-0001-9299-2534], Carracedo, Ángel [0000-0003-1085-8986], Ruiz, Agustín [0000-0003-2633-2495], Universidad de Cantabria, Rojas, Itziar de, Calero, Miguel, Menéndez-González, Manuel, Díez-Fairen, Mónica, Rábano, Alberto, Rodríguez-Rodríguez, Eloy, Álvarez, Ignacio, Bullido, María Jesús, Álvarez, Victoria, Real, Luis M., Medina, Miguel, Butler, Christopher R., Sáez, María Eugenia, Carracedo, Ángel, Ruiz, Agustín, and UAM. Departamento de Biología Molecular
Subjects: SARS-CoV-2, COVID-19, GWAS, GR@ACE/DEGESCO, dementia, APOE, Medicine (miscellaneous), Biología y Biomedicina / Biología, Article, Medicine
Abstract: Emerging studies have suggested several chromosomal regions as potential host genetic factors involved in the susceptibility to SARS-CoV-2 infection and disease outcome. We nested a COVID-19 genome-wide association study using the GR@ACE/DEGESCO study, searching for susceptibility factors associated with COVID-19 disease. To this end, we compared 221 COVID-19 confirmed cases with 17,035 individuals in whom the COVID-19 disease status was unknown. Then, we performed a meta-analysis with the publicly available data from the COVID-19 Host Genetics Initiative. Because the APOE locus has been suggested as a potential modifier of COVID-19 disease, we added sensitivity analyses stratifying by dementia status or by disease severity. We confirmed the existence of the 3p21.31 region (LZTFL1, SLC6A20) implicated in the susceptibility to SARS-CoV-2 infection and TYK2 gene might be involved in COVID-19 severity. Nevertheless, no statistically significant association was observed in the COVID-19 fatal outcome or in the stratified analyses (dementia-only and non-dementia strata) for the APOE locus not supporting its involvement in SARS-CoV-2 pathobiology or COVID-19 prognosis., We would like to thank patients and controls who participated in this project. The present work has been performed as part of the doctoral program of I. de Rojas at the Universitat de Barcelona (Barcelona, Spain) supported by national grant from the Instituto de Salud Carlos III FI20/00215. The Genome Research @ Fundació ACE project (GR@ACE) is supported by Grifols SA, Fundación bancaria ‘La Caixa’, Fundació ACE, and CIBERNED. The Vallecas Project is supported by Queen Sofia Foundation and the Instituto de Salud Carlos III. The position held by SA-L is funded by Instituto de Salud Carlos III (Co-funded by European Social Fund “Investing in your future”) Sara Borrell Contract (CD19/00232). A.R. and M.B. receive support from the European Union/EFPIA Innovative Medicines Initiative Joint undertaking ADAPTED and MOPEAD projects (grant numbers 115975 and 115985, respectively). M.B. and A.R. are also supported by national grants PI13/02434, PI16/01861, PI17/01474, PI19/01240 and PI19/01301. Acción Estratégica en Salud is integrated into the Spanish National R + D + I Plan and funded by ISCIII (Instituto de Salud Carlos III)–Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER–‘Una manera de hacer Europa’). Some control samples and data from patients included in this study were provided in part by the National DNA Bank Carlos III (www.bancoadn.org, accessed date: 1 October 2021, University of Salamanca, Spain) and Hospital Universitario Virgen de Valme (Sevilla, Spain); they were processed following standard operating procedures with the appropriate approval of the Ethical and Scientific Committee. This research has been conducted using the COVID-19 Host Genetic Initiative public resource obtained through the web site (https://www.covid19hg.org/results/, accessed date: 1 October 2021).
Published: 2021

33. Increased Stroke Risk in Patients with Parkinson's Disease withLRRK2Mutations

Author: Macías‐García, Daniel, primary, Periñán, María Teresa, additional, Muñoz‐Delgado, Laura, additional, Jesús, Silvia, additional, Jimenez‐Jaraba, María Valle, additional, Buiza‐Rueda, Dolores, additional, Bonilla‐Toribio, Marta, additional, Adarmes‐Gómez, Astrid, additional, Carrillo, Fátima, additional, Gómez‐Garre, Pilar, additional, and Mir, Pablo, additional
Published: 2021
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34. Intermediate and Expanded HTT Alleles and the Risk for α-Synucleinopathies.

Author: Pérez‐Oliveira, Sergio, Álvarez, Ignacio, Rosas, Irene, Menendez‐González, Manuel, Blázquez‐Estrada, Marta, Aguilar, Miquel, Corte, Daniela, Buongiorno, Mariateresa, Molina‐Porcel, Laura, Aldecoa, Iban, Martí, María J., Sánchez‐Juan, Pascual, Infante, Jon, González‐Aramburu, Isabel, García‐González, Pablo, Rosende‐Roca, Maitée, Boada, Mercè, Ruiz, Agustín, Periñán, María Teresa, and Macías‐García, Daniel
Subjects: DNA, ALLELES, PARKINSON'S disease, RESEARCH funding, HUNTINGTON disease, NEURODEGENERATION
Abstract: Background: Previous studies suggest a link between CAG repeat number in the HTT gene and non-Huntington neurodegenerative diseases.Objective: The aim is to analyze whether expanded HTT CAG alleles and/or their size are associated with the risk for developing α-synucleinopathies or their behavior as modulators of the phenotype.Methods: We genotyped the HTT gene CAG repeat number and APOE-Ɛ isoforms in a case-control series including patients with either clinical or neuropathological diagnosis of α-synucleinopathy.Results: We identified three Parkinson's disease (PD) patients (0.30%) and two healthy controls (0.19%) carrying low-penetrance HTT repeat expansions whereas none of the dementia with Lewy bodies (DLB) or multisystem atrophy (MSA) patients carried pathogenic HTT expansions. In addition, a clear increase in the number of HTT CAG repeats was found among DLB and PD groups influenced by the male gender and also by the APOE4 allele among DLB patients. HTT intermediate alleles' (IAs) distribution frequency increased in the MSA group compared with controls (8.8% vs. 3.9%, respectively). These differences were indeed statistically significant in the MSA group with neuropathological confirmation. Two MSA HTT CAG IAs carriers with 32 HTT CAG repeats showed isolated polyQ inclusions in pons and basal nuclei, which are two critical structures in the neurodegeneration of MSA.Conclusions: Our results point to a link between HTT CAG number, HTT IAs, and expanded HTT CAG repeats with other non-HD brain pathology and support the hypothesis that they can share common neurodegenerative pathways. © 2022 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]
Published: 2022
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35. Genomic Characterization of Host Factors Related to SARS-CoV-2 Infection in People with Dementia and Control Populations: The GR@ACE/DEGESCO Study

Author: Instituto de Salud Carlos III, Grifols, La Caixa, Ace Alzheimer Center Barcelona, Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas (España), Fundación Reina Sofía, European Commission, Rojas, Itziar de [0000-0002-2148-381X], Calero, Miguel [0000-0001-5366-3324], Menéndez-González, Manuel [0000-0002-5218-0774], Díez-Fairen, Mónica [0000-0003-1882-0309], Rábano, Alberto [0000-0001-9320-6566], Rodríguez-Rodríguez, Eloy [0000-0001-7742-677X], Álvarez, Ignacio [0000-0002-8537-3935], Bullido, María Jesús [0000-0002-6477-1117], Álvarez, Victoria [0000-0002-1916-2523], Real, Luis M. [0000-0003-4932-7429], Medina, Miguel [0000-0002-7016-5340], Butler, Christopher R. [0000-0002-7502-9284], Sáez, María Eugenia [0000-0001-9299-2534], Carracedo, Ángel [0000-0003-1085-8986], Ruiz, Agustín [0000-0003-2633-2495], Rojas, Itziar de, Hernández, Isabel, Montrreal, Laura, Quintela, Inés, Calero, Miguel, Royo, José Luis, Huerto Vilas, Raquel, González-Pérez, Antonio, Franco-Macías, Emilio, Macías Sánchez, Juan, Menéndez-González, Manuel, Frank-García, Ana, Díez-Fairen, Mónica, Lage, Carmen, García-Madrona, Sebastián, Aguilera, Nuria, García-González, Pablo, Puerta, Raquel, Sotolongo-Grau, Oscar, Alonso-Lana, Silvia, Rábano, Alberto, Arias Pastor, Alfonso, Pastor, Ana Belén, Corma-Gómez, Anaïs, Martin Montes, Ángel, Martínez Rodríguez, Carmen, Buiza-Rueda, Dolores, Periñán, María Teresa, Rodríguez-Rodríguez, Eloy, Álvarez, Ignacio, Rosas Allende, Irene, Pineda, Juan A., Bernal Sánchez-Arjona, María, Fernández-Fuertes, Marta, Mendoza, Silvia, Ser, Teodoro del, GR@ACE, DEGESCO Consortium, García-Ribas, Guillermo, Sánchez-Juan, Pascual, Pastor, Pau, Bullido, María Jesús, Álvarez, Victoria, Real, Luis Miguel, Mir, Pablo, Piñol-Ripoll, Gerard, García-Alberca, José María, Medina, Miguel, Orellana, Adelina, Butler, Christopher R., Marquié, Marta, Sáez, María Eugenia, Carracedo, Ángel, Tárraga, Lluís, Boada, Mercè, Ruiz, Agustín, Instituto de Salud Carlos III, Grifols, La Caixa, Ace Alzheimer Center Barcelona, Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas (España), Fundación Reina Sofía, European Commission, Rojas, Itziar de [0000-0002-2148-381X], Calero, Miguel [0000-0001-5366-3324], Menéndez-González, Manuel [0000-0002-5218-0774], Díez-Fairen, Mónica [0000-0003-1882-0309], Rábano, Alberto [0000-0001-9320-6566], Rodríguez-Rodríguez, Eloy [0000-0001-7742-677X], Álvarez, Ignacio [0000-0002-8537-3935], Bullido, María Jesús [0000-0002-6477-1117], Álvarez, Victoria [0000-0002-1916-2523], Real, Luis M. [0000-0003-4932-7429], Medina, Miguel [0000-0002-7016-5340], Butler, Christopher R. [0000-0002-7502-9284], Sáez, María Eugenia [0000-0001-9299-2534], Carracedo, Ángel [0000-0003-1085-8986], Ruiz, Agustín [0000-0003-2633-2495], Rojas, Itziar de, Hernández, Isabel, Montrreal, Laura, Quintela, Inés, Calero, Miguel, Royo, José Luis, Huerto Vilas, Raquel, González-Pérez, Antonio, Franco-Macías, Emilio, Macías Sánchez, Juan, Menéndez-González, Manuel, Frank-García, Ana, Díez-Fairen, Mónica, Lage, Carmen, García-Madrona, Sebastián, Aguilera, Nuria, García-González, Pablo, Puerta, Raquel, Sotolongo-Grau, Oscar, Alonso-Lana, Silvia, Rábano, Alberto, Arias Pastor, Alfonso, Pastor, Ana Belén, Corma-Gómez, Anaïs, Martin Montes, Ángel, Martínez Rodríguez, Carmen, Buiza-Rueda, Dolores, Periñán, María Teresa, Rodríguez-Rodríguez, Eloy, Álvarez, Ignacio, Rosas Allende, Irene, Pineda, Juan A., Bernal Sánchez-Arjona, María, Fernández-Fuertes, Marta, Mendoza, Silvia, Ser, Teodoro del, GR@ACE, DEGESCO Consortium, García-Ribas, Guillermo, Sánchez-Juan, Pascual, Pastor, Pau, Bullido, María Jesús, Álvarez, Victoria, Real, Luis Miguel, Mir, Pablo, Piñol-Ripoll, Gerard, García-Alberca, José María, Medina, Miguel, Orellana, Adelina, Butler, Christopher R., Marquié, Marta, Sáez, María Eugenia, Carracedo, Ángel, Tárraga, Lluís, Boada, Mercè, and Ruiz, Agustín
Abstract: Emerging studies have suggested several chromosomal regions as potential host genetic factors involved in the susceptibility to SARS-CoV-2 infection and disease outcome. We nested a COVID-19 genome-wide association study using the GR@ACE/DEGESCO study, searching for susceptibility factors associated with COVID-19 disease. To this end, we compared 221 COVID-19 confirmed cases with 17,035 individuals in whom the COVID-19 disease status was unknown. Then, we performed a meta-analysis with the publicly available data from the COVID-19 Host Genetics Initiative. Because the APOE locus has been suggested as a potential modifier of COVID-19 disease, we added sensitivity analyses stratifying by dementia status or by disease severity. We confirmed the existence of the 3p21.31 region (LZTFL1, SLC6A20) implicated in the susceptibility to SARS-CoV-2 infection and TYK2 gene might be involved in COVID-19 severity. Nevertheless, no statistically significant association was observed in the COVID-19 fatal outcome or in the stratified analyses (dementia-only and non-dementia strata) for the APOE locus not supporting its involvement in SARS-CoV-2 pathobiology or COVID-19 prognosis.
Published: 2021

36. Serum lipid profile among sporadic and familial forms of Parkinson’s disease

Author: Ministerio de Ciencia e Innovación (España), Instituto de Salud Carlos III, European Commission, Junta de Andalucía, Fundación Alicia Koplowitz, Ministerio de Educación, Cultura y Deporte (España), Macías García, Daniel, Periñán, María Teresa, Muñoz-Delgado, Laura, Jiménez-Jaraba, María Valle, Labrador, Miguel Ángel, Jesús Maestre, Silvia, Buiza-Rueda, Dolores, Méndez-Del Barrio, Carlota, Adarmes Gómez, A. D., Gómez-Garre, Pilar, Mir, Pablo, Ministerio de Ciencia e Innovación (España), Instituto de Salud Carlos III, European Commission, Junta de Andalucía, Fundación Alicia Koplowitz, Ministerio de Educación, Cultura y Deporte (España), Macías García, Daniel, Periñán, María Teresa, Muñoz-Delgado, Laura, Jiménez-Jaraba, María Valle, Labrador, Miguel Ángel, Jesús Maestre, Silvia, Buiza-Rueda, Dolores, Méndez-Del Barrio, Carlota, Adarmes Gómez, A. D., Gómez-Garre, Pilar, and Mir, Pablo
Abstract: Brain cholesterol metabolism has been described as altered in Parkinson’s disease (PD) patients. Serum lipid levels have been widely studied in PD with controversial results among different populations and age groups. The present study is aimed at determining if the serum lipid profile could be influenced by the genetic background of PD patients. We included 403 PD patients (342 sporadic PD patients, 30 GBA-associated PD patients, and 31 LRRK2-associated PD patients) and 654 healthy controls (HCs). Total cholesterol, HDL, LDL, and triglycerides were measured in peripheral blood. Analysis of covariance adjusting for sex and age (ANCOVA) and post hoc tests were applied to determine the differences within lipid profiles among the groups. Multivariate ANCOVA revealed significant differences among the groups within cholesterol and LDL levels. GBA-associated PD patients had significantly lower levels of total cholesterol and LDL compared to LRRK2-associated PD patients and HCs. The different serum cholesterol levels in GBA-associated PD might be related to diverse pathogenic mechanisms. Our results support the hypothesis of lipid metabolism disruption as one of the main PD pathogenic mechanisms in patients with GBA-associated PD. Further studies would be necessary to explore their clinical implications.
Published: 2021

37. The role of RHOT1 and RHOT2 genetic variation on Parkinson disease risk and onset

Author: National Institute of Neurological Disorders and Stroke (US), National Institute on Aging (US), National Institute of Environmental Health Sciences (US), National Institutes of Health (US), Department of Defense (US), Michael J. Fox Foundation for Parkinson's Research, Celgene, GlaxoSmithKline, Pfizer, Verily Life Sciences, Periñán, María Teresa, Gómez‐Garre, Pilar, Blauwendraat, Cornelis, Mir, Pablo, Bandres-Ciga, Sara, National Institute of Neurological Disorders and Stroke (US), National Institute on Aging (US), National Institute of Environmental Health Sciences (US), National Institutes of Health (US), Department of Defense (US), Michael J. Fox Foundation for Parkinson's Research, Celgene, GlaxoSmithKline, Pfizer, Verily Life Sciences, Periñán, María Teresa, Gómez‐Garre, Pilar, Blauwendraat, Cornelis, Mir, Pablo, and Bandres-Ciga, Sara
Abstract: Genetic variation within the mitochondrial pathway contributes to the risk of Parkinson’s disease (PD). Recent genetic analyses have investigated the association between the RHOT1 and RHOT2 genes and PD etiology. Furthermore, 4 mutations in the RHOT1 gene (p.R272Q, p.R450C, p.T351A, p.T610A) have been reported to be potentially associated with disease risk. As part of the International Parkinson Disease Genomics Consortium efforts to evaluate reported PD risk factors, we assessed the role of common and low frequency variants in both RHOT1 and also RHOT2 according to the high degree of homology in their amino acid sequences. Utilizing large-scale genotyping and whole-genome sequencing data from the International Parkinson Disease Genomics Consortium and the Accelerating Medicines Partnership – Parkinson Disease initiative, our analyses did not identify evidence to support the hypothesis that RHOT1 and RHOT2 are disease causing or modifying genes for PD risk or age at onset.
Published: 2021

38. Mutational spectrum of GNAL, THAP1 and TOR1A genes in isolated dystonia: study in a population from Spain and systematic literature review

Author: Instituto de Salud Carlos III, European Commission, Junta de Andalucía, Fundación Alicia Koplowitz, Fundación Mutua Madrileña, Universidad de Sevilla, Ministerio de Educación, Cultura y Deporte (España), Gómez-Garre, Pilar, Jesús Maestre, Silvia, Periñán, María Teresa, Adarmes Gómez, A. D., Alonso Cánovas, Araceli, Blanco-Ollero, Alberto, Buiza-Rueda, Dolores, Carrillo, Fátima, Catalán, M. J., Val, Javier del, Escamilla-Sevilla, Francisco, Espinosa-Rosso, Raúl, Fernández-Moreno, María Carmen, García Moreno, J. M., García-Ruiz, Pedro José, Giacometti-Silveira, Sandra, Gutiérrez-García, Javier, López-Valdés, Eva, Macías García, Daniel, Martínez-Castrillo, J. C., Martínez Torres, Irene, Medialdea-Natera, María Pilar, Mínguez-Castellanos, Adolfo, Moya, Miguel Ángel, Ochoa-Sepúlveda, Juan José, Ojea, Tomás, Rodríguez, Nuria, Sillero-Sánchez, Miriam, Tejera-Parrado, Cristina, Mir, Pablo, Instituto de Salud Carlos III, European Commission, Junta de Andalucía, Fundación Alicia Koplowitz, Fundación Mutua Madrileña, Universidad de Sevilla, Ministerio de Educación, Cultura y Deporte (España), Gómez-Garre, Pilar, Jesús Maestre, Silvia, Periñán, María Teresa, Adarmes Gómez, A. D., Alonso Cánovas, Araceli, Blanco-Ollero, Alberto, Buiza-Rueda, Dolores, Carrillo, Fátima, Catalán, M. J., Val, Javier del, Escamilla-Sevilla, Francisco, Espinosa-Rosso, Raúl, Fernández-Moreno, María Carmen, García Moreno, J. M., García-Ruiz, Pedro José, Giacometti-Silveira, Sandra, Gutiérrez-García, Javier, López-Valdés, Eva, Macías García, Daniel, Martínez-Castrillo, J. C., Martínez Torres, Irene, Medialdea-Natera, María Pilar, Mínguez-Castellanos, Adolfo, Moya, Miguel Ángel, Ochoa-Sepúlveda, Juan José, Ojea, Tomás, Rodríguez, Nuria, Sillero-Sánchez, Miriam, Tejera-Parrado, Cristina, and Mir, Pablo
Abstract: [Objective] We aimed to investigate the prevalence of TOR1A, GNAL and THAP1 variants as the cause of dystonia in a cohort of Spanish patients with isolated dystonia and in the literature., [Methods] A population of 2028 subjects (including 1053 patients with different subtypes of isolated dystonia and 975 healthy controls) from southern and central Spain was included. The genes TOR1A, THAP1 and GNAL were screened using a combination of high-resolution melting analysis and direct DNA resequencing. In addition, an extensive literature search to identify original articles (published before 10 August 2020) reporting mutations in TOR1A, THAP1 or GNAL associated to dystonia was performed., [Results] Pathogenic or likely pathogenic variants in TOR1A, THAP1 and GNAL were identified in 0.48%, 0.57% and 0.29% of our patients, respectively. Five patients carried the variation p.Glu303del in TOR1A. A very rare variant in GNAL (p.Ser238Asn) was found as a putative risk factor for dystonia. In the literature, variations in TOR1A, THAP1 and GNAL accounted for about 6%, 1.8% and 1.1% of published dystonia patients, respectively., [Conclusions] There is a different genetic contribution to dystonia of these three genes in our patients (about 1.3% of patients) and in the literature (about 3.6% of patients), probably due the high proportion of adult-onset cases in our cohort. As regards age at onset, site of dystonia onset, and final distribution, in our population there is a clear differentiation between DYT-TOR1A and DYT-GNAL, with DYT-THAP1 likely to be an intermediate phenotype.
Published: 2021

39. Integrating genetic and clinical data to predict impulse control disorders in Parkinson's disease

Author: Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, Junta de Andalucía, Sociedad Andaluza de Neurología, Fundación Alicia Koplowitz, Fundación Mutua Madrileña, Jacques and Gloria Gossweiler Foundation, Jesús Maestre, Silvia, Periñán, María Teresa, Cortés, C., Buiza-Rueda, Dolores, Macías García, Daniel, Adarmes Gómez, A. D., Muñoz‐Delgado, Laura, Labrador, Miguel Ángel, Tejera-Parrado, Cristina, Gómez-Garre, Pilar, Mir, Pablo, Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, Junta de Andalucía, Sociedad Andaluza de Neurología, Fundación Alicia Koplowitz, Fundación Mutua Madrileña, Jacques and Gloria Gossweiler Foundation, Jesús Maestre, Silvia, Periñán, María Teresa, Cortés, C., Buiza-Rueda, Dolores, Macías García, Daniel, Adarmes Gómez, A. D., Muñoz‐Delgado, Laura, Labrador, Miguel Ángel, Tejera-Parrado, Cristina, Gómez-Garre, Pilar, and Mir, Pablo
Abstract: [Background and purpose] Impulse control disorders (ICDs) are frequent in Parkinson’s disease (PD), with associated clinical and genetic risk factors. This study was aimed at analyzing the clinical features and the genetic background that underlie ICDs in PD., [Methods] We included 353 patients with PD in this study (58.9% men, mean age 62.4 ± 10.58 years, mean age at disease onset 52.71 ± 11.94 years). We used the validated Questionnaire for Impulsive–Compulsive Disorders in Parkinson’s Disease for ICDs screening. Motor, nonmotor, and treatment‐related features were evaluated according to the presence of ICDs. Twenty‐one variants related to dopaminergic, serotonergic, glutamatergic, and opioid neurotransmitter systems were assessed. Association studies between polymorphisms and ICDs were performed. The combination of clinical and genetic variables was analyzed with receiver operating characteristic curves to assess the predictability of experiencing ICDs., [Results] Impulse control disorders appeared in 25.1% of the cases. Patients with ICDs were younger and presented a higher rate of anxiety. Treatment with dopamine agonists increased the risk of ICDs and it was dose dependent (P < 0.05). Genetic association studies showed that the DOPA decarboxylase gene (DDC), rs1451375, might modulate the risk of ICDs. Plotting the clinical–genetic model, the predictability of ICDs increased 11% (area under curve = 0.80; z = 3.22, P = 0.001) when adding the genotype data for single nucleotide polymorphisms., [Conclusions] Polymorphisms in DDC might act as risk markers for ICDs in PD. The predictability of experiencing ICDs increased by adding genetic factors to clinical features. It is therefore important to assess the patient’s genetic background to identify individuals at risk for ICDs.
Published: 2021

40. A genetic analysis of a Spanish population with early onset Parkinson's disease

Author: Vela-Desojo Lydia, Miguel A. Labrador, Jesús Silvia, Bernal-Bernal Inmaculada, Huertas-Fernández Ismael, Periñán María Teresa, García-Ramos Rocío, Catalán-Alonso María José, Pilar Gómez-Garre, López-Manzanares Lydia, Mir Rivera Pablo, Buiza-Rueda Dolores, Del Val Javier, Ignacio J. Posada, Bonilla-Toribio Marta, Abreu-Rodríguez Irene, García-Ruiz Pedro José, Ruiz-Huete Cristina, Tejera-Parrado Cristina, Martínez-Castrillo Juan Carlos, Alonso-Cánovas Araceli, Rojo-Sebastián Ana, Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, European Commission, Junta de Andalucía, Sociedad Andaluza de Neurología, Fundación Alicia Koplowitz, Fundación Mutua Madrileña, and Universidad de Sevilla
Subjects: 0301 basic medicine, Male, Heredity, Epidemiology, Molecular biology, Disease, Geographical locations, Cohort Studies, Database and Informatics Methods, 0302 clinical medicine, Medical Conditions, Sequencing techniques, Medicine and Health Sciences, DNA sequencing, Age of Onset, Genetics, Multidisciplinary, Movement Disorders, Heterozygosity, medicine.diagnostic_test, High-Throughput Nucleotide Sequencing, Neurodegenerative Diseases, Parkinson Disease, Genomics, Middle Aged, LRRK2, Europe, Neurology, Medicine, Female, Transcriptome Analysis, Research Article, Next-Generation Sequencing, Adult, Bioinformatics, Science, PINK1, Research and Analysis Methods, 03 medical and health sciences, Genetic variation, medicine, Humans, European Union, Genetic Testing, Genetic testing, Biology and life sciences, business.industry, PARK7, Computational Biology, Correction, Genetic Variation, Human Genetics, Genome Analysis, Human genetics, nervous system diseases, 030104 developmental biology, Molecular biology techniques, Spain, Medical Risk Factors, Genetics of Disease, Age of onset, People and places, business, 030217 neurology & neurosurgery
Abstract: [Introduction] Both recessive and dominant genetic forms of Parkinson’s disease have been described. The aim of this study was to assess the contribution of several genes to the pathophysiology of early onset Parkinson’s disease in a cohort from central Spain., [Methods/patients] We analyzed a cohort of 117 unrelated patients with early onset Parkinson’s disease using a pipeline, based on a combination of a next-generation sequencing panel of 17 genes previously related with Parkinson’s disease and other Parkinsonisms and CNV screening., [Results] Twenty-six patients (22.22%) carried likely pathogenic variants in PARK2, LRRK2, PINK1, or GBA. The gene most frequently mutated was PARK2, and p.Asn52Metfs*29 was the most common variation in this gene. Pathogenic variants were not observed in genes SNCA, FBXO7, PARK7, HTRA2, DNAJC6, PLA2G6, and UCHL1. Co-occurrence of pathogenic variants involving two genes was observed in ATP13A2 and PARK2 genes, as well as LRRK2 and GIGYF2 genes., [Conclusions] Our results contribute to the understanding of the genetic architecture associated with early onset Parkinson’s disease, showing both PARK2 and LRRK2 play an important role in Spanish Parkinson’s disease patients. Rare variants in ATP13A2 and GIGYF2 may contribute to PD risk. However, a large proportion of genetic components remains unknown. This study might contribute to genetic diagnosis and counseling for families with early onset Parkinson’s disease., This study was supported by grants from the Spanish Ministry of Economy and Competitiveness [PI14/01823, PI16/01575, PI18/01898] co-founded by ISCIII (Subdirección General de Evaluación y Fomento de la Investigación) and by Fondo Europeo de Desarrollo Regional (FEDER), the Consejería de Economía, Innovación, Ciencia y Empleo de la Junta de Andalucía [CVI-02526, CTS-7685], the Consejería de Salud y Bienestar Social de la Junta de Andalucía [PI-0437-2012, PI-0471-2013], the Sociedad Andaluza de Neurología, the Fundación Alicia Koplowitz, the Fundación Mutua Madrileña. Pilar Gómez-Garre was supported by the "Miguel Servet" (from ISCIII-FEDER) and “Nicolás Monardes” (from Andalusian Ministry of Health) programs. Silvia Jesús Maestre was supported by the "Juan Rodés" program (from ISCIII-FEDER). Cristina Tejera was supported by VPPI-US from the Universidad de Sevilla.
Published: 2020

41. Analysis of p.Tyr307Asn variant in the LRP10 gene in Parkinson’s disease in southern Spain

Author: Instituto de Salud Carlos III, European Commission, Junta de Andalucía, Fundación Alicia Koplowitz, Ministerio de Educación, Cultura y Deporte (España), Periñán, María Teresa, Macías García, Daniel, Buiza-Rueda, Dolores, Guijarro-Albaladejo, Beatriz, Jesús Maestre, Silvia, Adarmes Gómez, A. D., Escuela, Rocío, Vigo-Ortega, Rosario, Gómez-Garre, Pilar, Mir, Pablo, Instituto de Salud Carlos III, European Commission, Junta de Andalucía, Fundación Alicia Koplowitz, Ministerio de Educación, Cultura y Deporte (España), Periñán, María Teresa, Macías García, Daniel, Buiza-Rueda, Dolores, Guijarro-Albaladejo, Beatriz, Jesús Maestre, Silvia, Adarmes Gómez, A. D., Escuela, Rocío, Vigo-Ortega, Rosario, Gómez-Garre, Pilar, and Mir, Pablo
Abstract: Lipoprotein receptor-related protein 10 (LRP10) has been proposed as a novel causative gene for autosomal dominant Parkinson’s disease (PD), and the c.919T>A (p.Tyr307Asn) variant has been identified as possibly involved in the development of familial PD and PD with dementia. We screened for the p.Tyr307Asn variant in a southern Spain population of 679 PD patients, of who 129 were familial cases, and 1217 unrelated healthy controls. A total of 3 carriers of the LRP10 p.Tyr307Asn variant were identified: 1 PD patient and 2 healthy controls. Together with the absence of a family history of PD, this finding might suggest a low penetrance variant as well as a limited role for p.Tyr307Asn in PD in our cohort. Nevertheless, a family history of Alzheimer’s disease in the LRP10 p.Tyr307Asn carriers provides evidence for a possible association with dementia.
Published: 2020

42. The Parkinson's Disease Genome‐Wide Association Study Locus Browser

Author: National Institute of Neurological Disorders and Stroke (US), National Institute on Aging (US), National Institute of Environmental Health Sciences (US), Medical Research Council (UK), Alzheimer's Research UK, Alzheimer Society, Cardiff University, European Commission, Welsh Government, National Heart, Lung, and Blood Institute (US), National Institutes of Health (US), Case Western Reserve University, Fondation Leducq, Cleveland Clinic, National Cancer Institute (US), Donald W. Reynolds Foundation, Amgen, Harris Family Foundation, Watkins Foundation, American Heart Association, COPD Foundation, National Human Genome Research Institute (US), Grenn, Francis P., Kim, Jonggeol J., Makarious, Mary B., Iwaki, Hirotaka, Illarionova, Anastasia, Brolin, Kajsa, Kluss, Jillian H., Schumacher‐Schuh, Artur F., Leonard, Hampton, Faghri, Faraz, Billingsley, Kimberley, Krohn, Lynne, Hall, Ashley, Díez-Fairen, Mónica, Periñán, María Teresa, Foo, Jia Nee, Sandor, Cynthia, Webber, Caleb, Fiske, Brian K., Gibbs, J. Raphael, Nalls, Mike A., Singleton, Andrew B., Bandres-Ciga, Sara, Reed, Xylena, Blauwendraat, Cornelis, National Institute of Neurological Disorders and Stroke (US), National Institute on Aging (US), National Institute of Environmental Health Sciences (US), Medical Research Council (UK), Alzheimer's Research UK, Alzheimer Society, Cardiff University, European Commission, Welsh Government, National Heart, Lung, and Blood Institute (US), National Institutes of Health (US), Case Western Reserve University, Fondation Leducq, Cleveland Clinic, National Cancer Institute (US), Donald W. Reynolds Foundation, Amgen, Harris Family Foundation, Watkins Foundation, American Heart Association, COPD Foundation, National Human Genome Research Institute (US), Grenn, Francis P., Kim, Jonggeol J., Makarious, Mary B., Iwaki, Hirotaka, Illarionova, Anastasia, Brolin, Kajsa, Kluss, Jillian H., Schumacher‐Schuh, Artur F., Leonard, Hampton, Faghri, Faraz, Billingsley, Kimberley, Krohn, Lynne, Hall, Ashley, Díez-Fairen, Mónica, Periñán, María Teresa, Foo, Jia Nee, Sandor, Cynthia, Webber, Caleb, Fiske, Brian K., Gibbs, J. Raphael, Nalls, Mike A., Singleton, Andrew B., Bandres-Ciga, Sara, Reed, Xylena, and Blauwendraat, Cornelis
Abstract: [Background] Parkinson's disease (PD) is a neurodegenerative disease with an often complex component identifiable by genome‐wide association studies. The most recent large‐scale PD genome‐wide association studies have identified more than 90 independent risk variants for PD risk and progression across more than 80 genomic regions. One major challenge in current genomics is the identification of the causal gene(s) and variant(s) at each genome‐wide association study locus. The objective of the current study was to create a tool that would display data for relevant PD risk loci and provide guidance with the prioritization of causal genes and potential mechanisms at each locus., [Methods] We included all significant genome‐wide signals from multiple recent PD genome‐wide association studies including themost recent PD risk genome‐wide association study, age‐at‐onset genome‐wide association study, progression genome‐wide association study, and Asian population PD risk genome‐wide association study. We gathered data for all genes 1 Mb up and downstream of each variant to allow users to assess which gene(s) are most associated with the variant of interest based on a set of self‐ranked criteria. Multiple databases were queried for each gene to collect additional causal data., [Results] We created a PD genome‐wide association study browser tool (https://pdgenetics.shinyapps.io/GWASBrowser/) to assist the PD research community with the prioritization of genes for follow‐up functional studies to identify potential therapeutic targets., [Conclusions] Our PD genome‐wide association study browser tool provides users with a useful method of identifying potential causal genes at all known PD risk loci from large‐scale PD genome‐wide association studies. We plan to update this tool with new relevant data as sample sizes increase and new PD risk loci are discovered. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by US Government employees and their work is in the public domain in the USA.
Published: 2020

43. A genetic analysis of a Spanish population with early onset Parkinson’s disease

Author: Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, European Commission, Junta de Andalucía, Sociedad Andaluza de Neurología, Fundación Alicia Koplowitz, Fundación Mutua Madrileña, Universidad de Sevilla, Tejera-Parrado, Cristina, Periñán, María Teresa, Vela-Desojo, Lydia, Abreu-Rodríguez, Irene, Alonso Cánovas, Araceli, Bernal-Bernal, Inmaculada, Bonilla-Toribio, Marta, Buiza-Rueda, Dolores, Catalán, M. J., García-Ramos, Rocío, García-Ruiz, Pedro José, Huertas-Fernández, Ismael, Silva-Rodríguez, Jesús, Labrador, Miguel Ángel, López-Manzanares, Lydia, Martínez-Castrillo, J. C., Posada, Ignacio J., Rojo-Sebastián, Ana, Ruiz-Huete, Cristina, Val, Javier del, Gómez-Garre, Pilar, Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, European Commission, Junta de Andalucía, Sociedad Andaluza de Neurología, Fundación Alicia Koplowitz, Fundación Mutua Madrileña, Universidad de Sevilla, Tejera-Parrado, Cristina, Periñán, María Teresa, Vela-Desojo, Lydia, Abreu-Rodríguez, Irene, Alonso Cánovas, Araceli, Bernal-Bernal, Inmaculada, Bonilla-Toribio, Marta, Buiza-Rueda, Dolores, Catalán, M. J., García-Ramos, Rocío, García-Ruiz, Pedro José, Huertas-Fernández, Ismael, Silva-Rodríguez, Jesús, Labrador, Miguel Ángel, López-Manzanares, Lydia, Martínez-Castrillo, J. C., Posada, Ignacio J., Rojo-Sebastián, Ana, Ruiz-Huete, Cristina, Val, Javier del, and Gómez-Garre, Pilar
Abstract: [Introduction] Both recessive and dominant genetic forms of Parkinson’s disease have been described. The aim of this study was to assess the contribution of several genes to the pathophysiology of early onset Parkinson’s disease in a cohort from central Spain., [Methods/patients] We analyzed a cohort of 117 unrelated patients with early onset Parkinson’s disease using a pipeline, based on a combination of a next-generation sequencing panel of 17 genes previously related with Parkinson’s disease and other Parkinsonisms and CNV screening., [Results] Twenty-six patients (22.22%) carried likely pathogenic variants in PARK2, LRRK2, PINK1, or GBA. The gene most frequently mutated was PARK2, and p.Asn52Metfs*29 was the most common variation in this gene. Pathogenic variants were not observed in genes SNCA, FBXO7, PARK7, HTRA2, DNAJC6, PLA2G6, and UCHL1. Co-occurrence of pathogenic variants involving two genes was observed in ATP13A2 and PARK2 genes, as well as LRRK2 and GIGYF2 genes., [Conclusions] Our results contribute to the understanding of the genetic architecture associated with early onset Parkinson’s disease, showing both PARK2 and LRRK2 play an important role in Spanish Parkinson’s disease patients. Rare variants in ATP13A2 and GIGYF2 may contribute to PD risk. However, a large proportion of genetic components remains unknown. This study might contribute to genetic diagnosis and counseling for families with early onset Parkinson’s disease.
Published: 2020

44. The role of RHOT1 and RHOT2 genetic variation on Parkinson disease risk and onset

Author: Periñán, María Teresa, primary, Gómez-Garre, Pilar, additional, Blauwendraat, Cornelis, additional, Mir, Pablo, additional, and Bandres-Ciga, Sara, additional
Published: 2021
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45. Mutational spectrum of GNAL , THAP1 and TOR1A genes in isolated dystonia: study in a population from Spain and systematic literature review

Author: Gómez‐Garre, Pilar, primary, Jesús, Silvia, additional, Periñán, María Teresa, additional, Adarmes, Astrid, additional, Alonso‐Canovas, Araceli, additional, Blanco‐Ollero, Alberto, additional, Buiza‐Rueda, Dolores, additional, Carrillo, Fátima, additional, Catalán‐Alonso, María José, additional, Val, Javier, additional, Escamilla‐Sevilla, Francisco, additional, Espinosa‐Rosso, Raúl, additional, Fernández‐Moreno, María Carmen, additional, García‐Moreno, José Manuel, additional, García‐Ruiz, Pedro José, additional, Giacometti‐Silveira, Sandra, additional, Gutiérrez‐García, Javier, additional, López‐Valdés, Eva, additional, Macías‐García, Daniel, additional, Martínez‐Castrillo, Juan Carlos, additional, Martínez‐Torres, Irene, additional, Medialdea‐Natera, María Pilar, additional, Mínguez‐Castellanos, Adolfo, additional, Moya, Miguel Ángel, additional, Ochoa‐Sepulveda, Juan José, additional, Ojea, Tomás, additional, Rodríguez, Nuria, additional, Sillero‐Sánchez, Miriam, additional, Tejera‐Parrado, Cristina, additional, and Mir, Pablo, additional
Published: 2020
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46. Association ofPICALMwith Cognitive Impairment in Parkinson's Disease

Author: Periñán, María Teresa, primary, Macías‐García, Daniel, additional, Labrador‐Espinosa, Miguel Ángel, additional, Jesús, Silvia, additional, Buiza‐Rueda, Dolores, additional, Adarmes‐Gómez, Astrid D., additional, Muñoz‐Delgado, Laura, additional, Gómez‐Garre, Pilar, additional, and Mir, Pablo, additional
Published: 2020
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47. The Genetic Architecture of Parkinson Disease in Spain: Characterizing Population-Specific Risk, Differential Haplotype Structures, and Providing Etiologic Insight

Author: National Institutes of Health (US), Department of Defense (US), Michael J. Fox Foundation for Parkinson's Research, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), European Commission, Junta de Andalucía, Sociedad Andaluza de Neurología, Jacques and Gloria Gossweiler Foundation, Fundación Alicia Koplowitz, Fundación Mutua Madrileña, Universidad de Sevilla, Bandres-Ciga, Sara, Ahmed, Sarah, Sabir, Marya S., Blauwendraat, Cornelis, Adarmes Gómez, A. D., Bernal-Bernal, Inmaculada, Bonilla-Toribio, Marta, Buiza-Rueda, Dolores, Carrillo, Fátima, Carrión-Claro, Mario, Gómez-Garre, Pilar, Jesús Maestre, Silvia, Labrador, Miguel Ángel, Macías García, Daniel, Méndez-Del Barrio, Carlota, Periñán, María Teresa, Tejera-Parrado, Cristina, Vargas-González, Laura, Díez-Fairen, Mónica, Álvarez, Ignacio, Tartari, J. P., Buongiorno, Maria Teresa, Aguilar, Miquel, Gorostidi, Ana, Bergareche, Jesús Alberto, Mondragon, Elisabet, Vinagre-Aragon, Ana, Croitoru, Ioana, Ruiz-Martínez, Javier, Dols-Icardo, Oriol, Kulisevsky, Jaime, Marín-Lahoz, Juan, Pagonabarraga-Mora, Javier, Pascual-Sedano, Berta, Ezquerra, Mario, Cámara, Ana, Compta, Yaroslau, Fernández Ortiga, Manel, Fernández-Santiago, Rubén, Muñoz, Esteban, Tolosa, Eduardo, Valldeoriola, Francesc, González-Aramburu, Isabel, Sanchez Rodriguez, Antonio, Sierra, María, Menéndez González, M., Blazquez, Marta, Garcia, Ciara, Suarez-San Martin, Esther, García-Ruíz, Pedro, Martínez-Castrillo, J. C., Vela-Desojo, Lydia, Ruz, Clara, Barrero, Francisco Javier, Escamilla-Sevilla, Francisco, Mínguez-Castellanos, Adolfo, Cerdan, Debora, Tabernero, César, Gomez Heredia, Maria Jose, Perez Errazquin, Francisco, Romero-Acebal, Manolo, Feliz, Cici, López-Sendón, José Luis, Mata, Marina, Martínez Torres, Irene, Kim, Jonggeol Jeffrey, Dalgard, Clifton L., Brooks, Janet, Saez-Atienzar, Sara, Gibbs, J. Raphael, Jorda, Rafael, Botia, Juan A., Bonet-Ponce, Luis, Morrison, Karen E., Clarke, Carl, Tan, Manuela, Morris, Huw, Edsall, Connor, Hernández, Dena, Simón-Sánchez, Javier, Nalls, Michael A., Scholz, Sonja, Jiménez Escrig, Adriano, Duarte, Jacinto, Vives, Francisco, Duran, Raquel, Hoenicka, Janet, Álvarez, Victoria, Infante, Jon, Martí, María-José, Clarimón, Jordi, López de Munain, Adolfo, Pastor, Pau, Mir, Pablo, Singleton, Andrew B., National Institutes of Health (US), Department of Defense (US), Michael J. Fox Foundation for Parkinson's Research, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), European Commission, Junta de Andalucía, Sociedad Andaluza de Neurología, Jacques and Gloria Gossweiler Foundation, Fundación Alicia Koplowitz, Fundación Mutua Madrileña, Universidad de Sevilla, Bandres-Ciga, Sara, Ahmed, Sarah, Sabir, Marya S., Blauwendraat, Cornelis, Adarmes Gómez, A. D., Bernal-Bernal, Inmaculada, Bonilla-Toribio, Marta, Buiza-Rueda, Dolores, Carrillo, Fátima, Carrión-Claro, Mario, Gómez-Garre, Pilar, Jesús Maestre, Silvia, Labrador, Miguel Ángel, Macías García, Daniel, Méndez-Del Barrio, Carlota, Periñán, María Teresa, Tejera-Parrado, Cristina, Vargas-González, Laura, Díez-Fairen, Mónica, Álvarez, Ignacio, Tartari, J. P., Buongiorno, Maria Teresa, Aguilar, Miquel, Gorostidi, Ana, Bergareche, Jesús Alberto, Mondragon, Elisabet, Vinagre-Aragon, Ana, Croitoru, Ioana, Ruiz-Martínez, Javier, Dols-Icardo, Oriol, Kulisevsky, Jaime, Marín-Lahoz, Juan, Pagonabarraga-Mora, Javier, Pascual-Sedano, Berta, Ezquerra, Mario, Cámara, Ana, Compta, Yaroslau, Fernández Ortiga, Manel, Fernández-Santiago, Rubén, Muñoz, Esteban, Tolosa, Eduardo, Valldeoriola, Francesc, González-Aramburu, Isabel, Sanchez Rodriguez, Antonio, Sierra, María, Menéndez González, M., Blazquez, Marta, Garcia, Ciara, Suarez-San Martin, Esther, García-Ruíz, Pedro, Martínez-Castrillo, J. C., Vela-Desojo, Lydia, Ruz, Clara, Barrero, Francisco Javier, Escamilla-Sevilla, Francisco, Mínguez-Castellanos, Adolfo, Cerdan, Debora, Tabernero, César, Gomez Heredia, Maria Jose, Perez Errazquin, Francisco, Romero-Acebal, Manolo, Feliz, Cici, López-Sendón, José Luis, Mata, Marina, Martínez Torres, Irene, Kim, Jonggeol Jeffrey, Dalgard, Clifton L., Brooks, Janet, Saez-Atienzar, Sara, Gibbs, J. Raphael, Jorda, Rafael, Botia, Juan A., Bonet-Ponce, Luis, Morrison, Karen E., Clarke, Carl, Tan, Manuela, Morris, Huw, Edsall, Connor, Hernández, Dena, Simón-Sánchez, Javier, Nalls, Michael A., Scholz, Sonja, Jiménez Escrig, Adriano, Duarte, Jacinto, Vives, Francisco, Duran, Raquel, Hoenicka, Janet, Álvarez, Victoria, Infante, Jon, Martí, María-José, Clarimón, Jordi, López de Munain, Adolfo, Pastor, Pau, Mir, Pablo, and Singleton, Andrew B.
Abstract: Background: The Iberian Peninsula stands out as having variable levels of population admixture and isolation, making Spain an interesting setting for studying the genetic architecture of neurodegenerative diseases. Objectives: To perform the largest PD genome-wide association study restricted to a single country. Methods: We performed a GWAS for both risk of PD and age at onset in 7,849 Spanish individuals. Further analyses included population-specific risk haplotype assessments, polygenic risk scoring through machine learning, Mendelian randomization of expression, and methylation data to gain insight into disease-associated loci, heritability estimates, genetic correlations, and burden analyses. Results: We identified a novel population-specific genome-wide association study signal at PARK2 associated with age at onset, which was likely dependent on the c.155delA mutation. We replicated four genome-wide independent signals associated with PD risk, including SNCA, LRRK2, KANSL1/MAPT, and HLA-DQB1. A significant trend for smaller risk haplotypes at known loci was found compared to similar studies of non-Spanish origin. Seventeen PD-related genes showed functional consequence by two-sample Mendelian randomization in expression and methylation data sets. Long runs of homozygosity at 28 known genes/loci were found to be enriched in cases versus controls. Conclusions: Our data demonstrate the utility of the Spanish risk haplotype substructure for future fine-mapping efforts, showing how leveraging unique and diverse population histories can benefit genetic studies of complex diseases. The present study points to PARK2 as a major hallmark of PD etiology in Spain.
Published: 2019

48. A replication study of GWAS-genetic risk variants associated with Parkinson’s disease in a Spanish population

Author: Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, European Commission, Junta de Andalucía, Sociedad Andaluza de Neurología, Jacques and Gloria Gossweiler Foundation, Fundación Alicia Koplowitz, Fundación Mutua Madrileña, Universidad de Sevilla, Tejera-Parrado, Cristina, Jesús Maestre, Silvia, Periñán, María Teresa, Buiza-Rueda, Dolores, Oliva-Ariza, Guillermo, Adarmes Gómez, A. D., Macías García, Daniel, Gómez-Garre, Pilar, Mir, Pablo, Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, European Commission, Junta de Andalucía, Sociedad Andaluza de Neurología, Jacques and Gloria Gossweiler Foundation, Fundación Alicia Koplowitz, Fundación Mutua Madrileña, Universidad de Sevilla, Tejera-Parrado, Cristina, Jesús Maestre, Silvia, Periñán, María Teresa, Buiza-Rueda, Dolores, Oliva-Ariza, Guillermo, Adarmes Gómez, A. D., Macías García, Daniel, Gómez-Garre, Pilar, and Mir, Pablo
Abstract: Recently, 5 previously Parkinson’s disease (PD)-related loci: ACMSD/TMEM163, STK39, MIR4697, SREBF1/RAI1PD and MAPT, have been associated to PD in a Southern Spanish population. However, due to the small sample size of the cohort, this association did not reach genome wide significance. Our aim was to investigate the robustness of this association in a larger and independent cohort from the South of Spain. Variants were genotyped employing TaqMan SNP Genotyping Assay and high resolution melting analysis in 738 PD patients and 1138 healthy controls. Furthermore, a meta-analysis study was carried out with both cohorts. In the replication analysis, only two loci (ACMSD/TMEM163 and MAPT) were replicated with a Bonferroni significance level. In the meta-analysis study no loci reached a genome-wide significance level (P<5xE-8), but a suggestive association (P-value = 1.04E-6) between rs6430538 (ACMSD/TMEM163) and an increased risk of PD was found. In addition, rs9468 (MAPT) was associated with a decreased risk of PD (P-value = 5.70E-7). Our results add further support for the genetic involvement of these two loci in the susceptibility to PD in population from the South of Spain. We believe that our findings will be very useful for future genetic studies on PD.
Published: 2019

49. A replication study of GWAS-genetic risk variants associated with Parkinson’s disease in a Spanish population

Author: Tejera-Parrado, Cristina, primary, Jesús, Silvia, additional, Periñán, María Teresa, additional, Buiza-Rueda, Dolores, additional, Oliva-Ariza, Guillermo, additional, Adarmes-Gómez, Astrid D, additional, Macías-García, Daniel, additional, Gómez-Garre, Pilar, additional, and Mir, Pablo, additional
Published: 2019
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50. Mutational spectrum of GNAL, THAP1 and TOR1A genes in isolated dystonia: study in a population from Spain and systematic literature review.

Author: Gómez‐Garre, Pilar, Jesús, Silvia, Periñán, María Teresa, Adarmes, Astrid, Alonso‐Canovas, Araceli, Blanco‐Ollero, Alberto, Buiza‐Rueda, Dolores, Carrillo, Fátima, Catalán‐Alonso, María José, Val, Javier, Escamilla‐Sevilla, Francisco, Espinosa‐Rosso, Raúl, Fernández‐Moreno, María Carmen, García‐Moreno, José Manuel, García‐Ruiz, Pedro José, Giacometti‐Silveira, Sandra, Gutiérrez‐García, Javier, López‐Valdés, Eva, Macías‐García, Daniel, and Martínez‐Castrillo, Juan Carlos
Subjects: GENES, DYSTONIA, DNA analysis, AGE of onset
Abstract: Objective: We aimed to investigate the prevalence of TOR1A, GNAL and THAP1 variants as the cause of dystonia in a cohort of Spanish patients with isolated dystonia and in the literature. Methods: A population of 2028 subjects (including 1053 patients with different subtypes of isolated dystonia and 975 healthy controls) from southern and central Spain was included. The genes TOR1A, THAP1 and GNAL were screened using a combination of high‐resolution melting analysis and direct DNA resequencing. In addition, an extensive literature search to identify original articles (published before 10 August 2020) reporting mutations in TOR1A, THAP1 or GNAL associated to dystonia was performed. Results: Pathogenic or likely pathogenic variants in TOR1A, THAP1 and GNAL were identified in 0.48%, 0.57% and 0.29% of our patients, respectively. Five patients carried the variation p.Glu303del in TOR1A. A very rare variant in GNAL (p.Ser238Asn) was found as a putative risk factor for dystonia. In the literature, variations in TOR1A, THAP1 and GNAL accounted for about 6%, 1.8% and 1.1% of published dystonia patients, respectively. Conclusions: There is a different genetic contribution to dystonia of these three genes in our patients (about 1.3% of patients) and in the literature (about 3.6% of patients), probably due the high proportion of adult‐onset cases in our cohort. As regards age at onset, site of dystonia onset, and final distribution, in our population there is a clear differentiation between DYT‐TOR1A and DYT‐GNAL, with DYT‐THAP1 likely to be an intermediate phenotype. [ABSTRACT FROM AUTHOR]
Published: 2021
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