Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- Autores
- de Rojas, Itziar; Moreno Grau, Sonia; Tesi, Niccolo; Grenier Boley, Benjamin; Andrade, Victor; Pedersen, Nancy L.; Stringa, Najada; Zettergren, Anna; Hernández, Isabel; Montrreal, Laura; Antúnez, Carmen; Antonell, Anna; Tankard, Rick M.; Bis, Joshua C.; Sims, Rebecca; Bellenguez, Céline; Quintela, Inés; González Perez, Antonio; Calero, Miguel; Franco Macías, Emilio; Macías, Juan; Blesa, Rafael; Cervera Carles, Laura; Menéndez González, Manuel; Frank García, Ana; Royo, Jose Luís; Moreno, Fermin; Huerto Vilas, Raquel; Baquero, Miquel; Dalmasso, Maria Carolina
- Año de publicación
- 2021
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease.
Fil: de Rojas, Itziar. Universitat Internacional de Catalunya; España. Instituto de Salud Carlos Iii (isciii); España
Fil: Moreno Grau, Sonia. Universitat Internacional de Catalunya; España. Instituto de Salud Carlos Iii (isciii); España
Fil: Tesi, Niccolo. Vrije Universiteit Amsterdam; Países Bajos. Delft University of Technology; Países Bajos
Fil: Grenier Boley, Benjamin. Universite Lille; Francia
Fil: Andrade, Victor. Universitat zu Köln; Alemania. Universitat Bonn; Alemania
Fil: Pedersen, Nancy L.. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Fil: Stringa, Najada. University of Amsterdam; Países Bajos
Fil: Zettergren, Anna. University of Gothenburg; Suecia
Fil: Hernández, Isabel. Universitat Internacional de Catalunya; España. Instituto de Salud Carlos Iii (isciii); España
Fil: Montrreal, Laura. Universitat Internacional de Catalunya; España
Fil: Antúnez, Carmen. Hospital Clínico Universitario Virgen de la Arrixaca; España
Fil: Antonell, Anna. Universidad de Barcelona; España
Fil: Tankard, Rick M.. Murdoch University; Australia
Fil: Bis, Joshua C.. University of Washington; Estados Unidos
Fil: Sims, Rebecca. Cardiff University; Reino Unido
Fil: Bellenguez, Céline. Universite Lille; Francia
Fil: Quintela, Inés. Universidad de Santiago de Compostela; España
Fil: González Perez, Antonio. Centro Andaluz de Estudios Bioinformáticos; España
Fil: Calero, Miguel. Instituto de Salud Carlos Iii (isciii); España. Fundación Reina Sofia; España
Fil: Franco Macías, Emilio. Universidad de Sevilla; España
Fil: Macías, Juan. Hospital Universitario de Valme; España
Fil: Blesa, Rafael. Instituto de Salud Carlos Iii (isciii); España. Universitat Autònoma de Barcelona; España
Fil: Cervera Carles, Laura. Instituto de Salud Carlos Iii (isciii); España. Universitat Autònoma de Barcelona; España
Fil: Menéndez González, Manuel. Universidad de Oviedo; España
Fil: Frank García, Ana. Instituto de Salud Carlos Iii (isciii); España. Universidad Autónoma de Madrid; España. Instituto de Investigacion del Hospital de la Paz.; España. Hospital Universitario La Paz; España
Fil: Royo, Jose Luís. Universidad de Málaga; España
Fil: Moreno, Fermin. Instituto de Salud Carlos Iii (isciii); España. Hospital Universitario Donostia; España. Instituto Biodonostia; España
Fil: Huerto Vilas, Raquel. Hospital Universitari Santa Maria de Lleida; España. Institut de Recerca Biomedica de Lleida; España
Fil: Baquero, Miquel. Hospital Universitari i Politècnic La Fe; España
Fil: Dalmasso, Maria Carolina. Gobierno de la Provincia de la Pampa. Ministerio Publico. Laboratorio de Genetica Forense.; Argentina. Universitat zu Köln; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Confluencia; Argentina - Materia
-
ALZHEIMER DISEASE
GENOME WIDE ASSOCIATION STUDY
POLYGENIC RISK SCORE - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/149959
Ver los metadatos del registro completo
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scoresde Rojas, ItziarMoreno Grau, SoniaTesi, NiccoloGrenier Boley, BenjaminAndrade, VictorPedersen, Nancy L.Stringa, NajadaZettergren, AnnaHernández, IsabelMontrreal, LauraAntúnez, CarmenAntonell, AnnaTankard, Rick M.Bis, Joshua C.Sims, RebeccaBellenguez, CélineQuintela, InésGonzález Perez, AntonioCalero, MiguelFranco Macías, EmilioMacías, JuanBlesa, RafaelCervera Carles, LauraMenéndez González, ManuelFrank García, AnaRoyo, Jose LuísMoreno, FerminHuerto Vilas, RaquelBaquero, MiquelDalmasso, Maria CarolinaALZHEIMER DISEASEGENOME WIDE ASSOCIATION STUDYPOLYGENIC RISK SCOREhttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease.Fil: de Rojas, Itziar. Universitat Internacional de Catalunya; España. Instituto de Salud Carlos Iii (isciii); EspañaFil: Moreno Grau, Sonia. Universitat Internacional de Catalunya; España. Instituto de Salud Carlos Iii (isciii); EspañaFil: Tesi, Niccolo. Vrije Universiteit Amsterdam; Países Bajos. Delft University of Technology; Países BajosFil: Grenier Boley, Benjamin. Universite Lille; FranciaFil: Andrade, Victor. Universitat zu Köln; Alemania. Universitat Bonn; AlemaniaFil: Pedersen, Nancy L.. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Stringa, Najada. University of Amsterdam; Países BajosFil: Zettergren, Anna. University of Gothenburg; SueciaFil: Hernández, Isabel. Universitat Internacional de Catalunya; España. Instituto de Salud Carlos Iii (isciii); EspañaFil: Montrreal, Laura. Universitat Internacional de Catalunya; EspañaFil: Antúnez, Carmen. Hospital Clínico Universitario Virgen de la Arrixaca; EspañaFil: Antonell, Anna. Universidad de Barcelona; EspañaFil: Tankard, Rick M.. Murdoch University; AustraliaFil: Bis, Joshua C.. University of Washington; Estados UnidosFil: Sims, Rebecca. Cardiff University; Reino UnidoFil: Bellenguez, Céline. Universite Lille; FranciaFil: Quintela, Inés. Universidad de Santiago de Compostela; EspañaFil: González Perez, Antonio. Centro Andaluz de Estudios Bioinformáticos; EspañaFil: Calero, Miguel. Instituto de Salud Carlos Iii (isciii); España. Fundación Reina Sofia; EspañaFil: Franco Macías, Emilio. Universidad de Sevilla; EspañaFil: Macías, Juan. Hospital Universitario de Valme; EspañaFil: Blesa, Rafael. Instituto de Salud Carlos Iii (isciii); España. Universitat Autònoma de Barcelona; EspañaFil: Cervera Carles, Laura. Instituto de Salud Carlos Iii (isciii); España. Universitat Autònoma de Barcelona; EspañaFil: Menéndez González, Manuel. Universidad de Oviedo; EspañaFil: Frank García, Ana. Instituto de Salud Carlos Iii (isciii); España. Universidad Autónoma de Madrid; España. Instituto de Investigacion del Hospital de la Paz.; España. Hospital Universitario La Paz; EspañaFil: Royo, Jose Luís. Universidad de Málaga; EspañaFil: Moreno, Fermin. Instituto de Salud Carlos Iii (isciii); España. Hospital Universitario Donostia; España. Instituto Biodonostia; EspañaFil: Huerto Vilas, Raquel. Hospital Universitari Santa Maria de Lleida; España. Institut de Recerca Biomedica de Lleida; EspañaFil: Baquero, Miquel. Hospital Universitari i Politècnic La Fe; EspañaFil: Dalmasso, Maria Carolina. Gobierno de la Provincia de la Pampa. Ministerio Publico. Laboratorio de Genetica Forense.; Argentina. Universitat zu Köln; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Confluencia; ArgentinaSpringer2021-06-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/149959de Rojas, Itziar; Moreno Grau, Sonia; Tesi, Niccolo; Grenier Boley, Benjamin; Andrade, Victor; et al.; Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores; Springer; Nature Communications; 12; 1; 7-6-2021; 1-162041-1723CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.nature.com/articles/s41467-021-22491-8info:eu-repo/semantics/altIdentifier/doi/10.1038/s41467-021-22491-8info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:36:05Zoai:ri.conicet.gov.ar:11336/149959instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:36:05.617CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores |
| title |
Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores |
| spellingShingle |
Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores de Rojas, Itziar ALZHEIMER DISEASE GENOME WIDE ASSOCIATION STUDY POLYGENIC RISK SCORE |
| title_short |
Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores |
| title_full |
Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores |
| title_fullStr |
Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores |
| title_full_unstemmed |
Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores |
| title_sort |
Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores |
| dc.creator.none.fl_str_mv |
de Rojas, Itziar Moreno Grau, Sonia Tesi, Niccolo Grenier Boley, Benjamin Andrade, Victor Pedersen, Nancy L. Stringa, Najada Zettergren, Anna Hernández, Isabel Montrreal, Laura Antúnez, Carmen Antonell, Anna Tankard, Rick M. Bis, Joshua C. Sims, Rebecca Bellenguez, Céline Quintela, Inés González Perez, Antonio Calero, Miguel Franco Macías, Emilio Macías, Juan Blesa, Rafael Cervera Carles, Laura Menéndez González, Manuel Frank García, Ana Royo, Jose Luís Moreno, Fermin Huerto Vilas, Raquel Baquero, Miquel Dalmasso, Maria Carolina |
| author |
de Rojas, Itziar |
| author_facet |
de Rojas, Itziar Moreno Grau, Sonia Tesi, Niccolo Grenier Boley, Benjamin Andrade, Victor Pedersen, Nancy L. Stringa, Najada Zettergren, Anna Hernández, Isabel Montrreal, Laura Antúnez, Carmen Antonell, Anna Tankard, Rick M. Bis, Joshua C. Sims, Rebecca Bellenguez, Céline Quintela, Inés González Perez, Antonio Calero, Miguel Franco Macías, Emilio Macías, Juan Blesa, Rafael Cervera Carles, Laura Menéndez González, Manuel Frank García, Ana Royo, Jose Luís Moreno, Fermin Huerto Vilas, Raquel Baquero, Miquel Dalmasso, Maria Carolina |
| author_role |
author |
| author2 |
Moreno Grau, Sonia Tesi, Niccolo Grenier Boley, Benjamin Andrade, Victor Pedersen, Nancy L. Stringa, Najada Zettergren, Anna Hernández, Isabel Montrreal, Laura Antúnez, Carmen Antonell, Anna Tankard, Rick M. Bis, Joshua C. Sims, Rebecca Bellenguez, Céline Quintela, Inés González Perez, Antonio Calero, Miguel Franco Macías, Emilio Macías, Juan Blesa, Rafael Cervera Carles, Laura Menéndez González, Manuel Frank García, Ana Royo, Jose Luís Moreno, Fermin Huerto Vilas, Raquel Baquero, Miquel Dalmasso, Maria Carolina |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
ALZHEIMER DISEASE GENOME WIDE ASSOCIATION STUDY POLYGENIC RISK SCORE |
| topic |
ALZHEIMER DISEASE GENOME WIDE ASSOCIATION STUDY POLYGENIC RISK SCORE |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.4 https://purl.org/becyt/ford/3 |
| dc.description.none.fl_txt_mv |
Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. Fil: de Rojas, Itziar. Universitat Internacional de Catalunya; España. Instituto de Salud Carlos Iii (isciii); España Fil: Moreno Grau, Sonia. Universitat Internacional de Catalunya; España. Instituto de Salud Carlos Iii (isciii); España Fil: Tesi, Niccolo. Vrije Universiteit Amsterdam; Países Bajos. Delft University of Technology; Países Bajos Fil: Grenier Boley, Benjamin. Universite Lille; Francia Fil: Andrade, Victor. Universitat zu Köln; Alemania. Universitat Bonn; Alemania Fil: Pedersen, Nancy L.. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia Fil: Stringa, Najada. University of Amsterdam; Países Bajos Fil: Zettergren, Anna. University of Gothenburg; Suecia Fil: Hernández, Isabel. Universitat Internacional de Catalunya; España. Instituto de Salud Carlos Iii (isciii); España Fil: Montrreal, Laura. Universitat Internacional de Catalunya; España Fil: Antúnez, Carmen. Hospital Clínico Universitario Virgen de la Arrixaca; España Fil: Antonell, Anna. Universidad de Barcelona; España Fil: Tankard, Rick M.. Murdoch University; Australia Fil: Bis, Joshua C.. University of Washington; Estados Unidos Fil: Sims, Rebecca. Cardiff University; Reino Unido Fil: Bellenguez, Céline. Universite Lille; Francia Fil: Quintela, Inés. Universidad de Santiago de Compostela; España Fil: González Perez, Antonio. Centro Andaluz de Estudios Bioinformáticos; España Fil: Calero, Miguel. Instituto de Salud Carlos Iii (isciii); España. Fundación Reina Sofia; España Fil: Franco Macías, Emilio. Universidad de Sevilla; España Fil: Macías, Juan. Hospital Universitario de Valme; España Fil: Blesa, Rafael. Instituto de Salud Carlos Iii (isciii); España. Universitat Autònoma de Barcelona; España Fil: Cervera Carles, Laura. Instituto de Salud Carlos Iii (isciii); España. Universitat Autònoma de Barcelona; España Fil: Menéndez González, Manuel. Universidad de Oviedo; España Fil: Frank García, Ana. Instituto de Salud Carlos Iii (isciii); España. Universidad Autónoma de Madrid; España. Instituto de Investigacion del Hospital de la Paz.; España. Hospital Universitario La Paz; España Fil: Royo, Jose Luís. Universidad de Málaga; España Fil: Moreno, Fermin. Instituto de Salud Carlos Iii (isciii); España. Hospital Universitario Donostia; España. Instituto Biodonostia; España Fil: Huerto Vilas, Raquel. Hospital Universitari Santa Maria de Lleida; España. Institut de Recerca Biomedica de Lleida; España Fil: Baquero, Miquel. Hospital Universitari i Politècnic La Fe; España Fil: Dalmasso, Maria Carolina. Gobierno de la Provincia de la Pampa. Ministerio Publico. Laboratorio de Genetica Forense.; Argentina. Universitat zu Köln; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Confluencia; Argentina |
| description |
Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. |
| publishDate |
2021 |
| dc.date.none.fl_str_mv |
2021-06-07 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/149959 de Rojas, Itziar; Moreno Grau, Sonia; Tesi, Niccolo; Grenier Boley, Benjamin; Andrade, Victor; et al.; Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores; Springer; Nature Communications; 12; 1; 7-6-2021; 1-16 2041-1723 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/149959 |
| identifier_str_mv |
de Rojas, Itziar; Moreno Grau, Sonia; Tesi, Niccolo; Grenier Boley, Benjamin; Andrade, Victor; et al.; Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores; Springer; Nature Communications; 12; 1; 7-6-2021; 1-16 2041-1723 CONICET Digital CONICET |
| dc.language.none.fl_str_mv |
eng |
| language |
eng |
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info:eu-repo/semantics/altIdentifier/url/http://www.nature.com/articles/s41467-021-22491-8 info:eu-repo/semantics/altIdentifier/doi/10.1038/s41467-021-22491-8 |
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info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by/2.5/ar/ |
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openAccess |
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https://creativecommons.org/licenses/by/2.5/ar/ |
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application/pdf application/pdf |
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Springer |
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Springer |
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dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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13.22299 |