The first genome‐wide association study in the Argentinian and Chilean populations identifies shared genetics with Europeans in Alzheimer's disease
- Autores
- Dalmasso, Maria Carolina; de Rojas, Itziar; Olivar, Natividad; Muchnik, Carolina; Angel, Bárbara; Gloger, Sergio; Sanchez Abalos, Mariana Soledad; Chacón, María Victoria; Aránguiz, Rafael; Orellana, Paulina; Cuesta, Carolina; Galeano, Pablo; Campanelli, Lorenzo; Novack, Gisela Vanina; Martinez, Luis Eduardo; Medel, Nancy Ruth; Lisso, Julieta; Sevillano, Zulma Haidée; Irureta, Nicolás; Castaño, Eduardo Miguel; Montrreal, Laura; Thoenes, Michaela; Hanses, Claudia; Heilmann-Heimbach, Stefanie; Fuentes, Patricio; Kochen, Silvia; Brusco, Luis Ignacio; Ruiz, Agustín; Morelli, Laura; Achitte, Eduardo Alfredo
- Año de publicación
- 2023
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- INTRODUCTION Genome-wide association studies (GWAS) are fundamental for identifying loci associated with diseases. However, they require replication in other ethnicities. METHODS We performed GWAS on sporadic Alzheimer's disease (AD) including 539 patients and 854 controls from Argentina and Chile. We combined our results with those from the European Alzheimer and Dementia Biobank (EADB) in a meta-analysis and tested their genetic risk score (GRS) performance in this admixed population. RESULTS We detected apolipoprotein E ε4 as the single genome-wide significant signal (odds ratio = 2.93 [2.37–3.63], P = 2.6 × 10−23). The meta-analysis with EADB summary statistics revealed four new loci reaching GWAS significance. Functional annotations of these loci implicated endosome/lysosomal function. Finally, the AD-GRS presented a similar performance in these populations, despite the score diminished when the Native American ancestry rose. DISCUSSION We report the first GWAS on AD in a population from South America. It shows shared genetics modulating AD risk between the European and these admixed populations. Highlights This is the first genome-wide association study on Alzheimer's disease (AD) in a population sample from Argentina and Chile. Trans-ethnic meta-analysis reveals four new loci involving lysosomal function in AD. This is the first independent replication for TREM2L, IGH-gene-cluster, and ADAM17 loci. A genetic risk score (GRS) developed in Europeans performed well in this population. The higher the Native American ancestry the lower the GRS values.
Fil: Dalmasso, Maria Carolina. Universidad Nacional Arturo Jauretche; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: de Rojas, Itziar. Universitat Internacional de Catalunya; España. Instituto de Salud Carlos III; España
Fil: Olivar, Natividad. Universidad de Buenos Aires; Argentina
Fil: Muchnik, Carolina. Universidad de Buenos Aires; Argentina
Fil: Angel, Bárbara. Universidad de Buenos Aires; Argentina
Fil: Gloger, Sergio. Universidad de Chile; Chile
Fil: Sanchez Abalos, Mariana Soledad. Interuniversity Center For Healthy Aging; Chile
Fil: Chacón, María Victoria. Centro Internacional de Estudios Clinicos; Chile
Fil: Aránguiz, Rafael. Universidad de Chile; Chile
Fil: Orellana, Paulina. Hospital Regional de Ushuaia; Argentina
Fil: Cuesta, Carolina. Centro Internacional de Estudios Clinicos; Chile
Fil: Galeano, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Campanelli, Lorenzo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Novack, Gisela Vanina. Universidad Adolfo Ibañez; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Martinez, Luis Eduardo. Hospital Interzonal General de Agudos-Eva Perón; Argentina
Fil: Medel, Nancy Ruth. Hospital Regional de Agudos Eva Perón (formerly Castex); Argentina
Fil: Lisso, Julieta. Fundacion Instituto Leloir Antigua Fundacion Campomar; Argentina
Fil: Sevillano, Zulma Haidée. Fundacion Instituto Leloir Antigua Fundacion Campomar; Argentina
Fil: Irureta, Nicolás. Fundacion Instituto Leloir Antigua Fundacion Campomar; Argentina
Fil: Castaño, Eduardo Miguel. Hospital Regional de Agudos Eva Perón (formerly Castex); Argentina
Fil: Montrreal, Laura. Hospital El Cruce; Argentina
Fil: Thoenes, Michaela. Studies In Neuroscience And Complex Systems Unit (enys-conicet-hec-unaj). Florencio Varela; Argentina
Fil: Hanses, Claudia. Studies In Neuroscience And Complex Systems Unit (enys-conicet-hec-unaj). Florencio Varela; Argentina
Fil: Heilmann-Heimbach, Stefanie. Hospital El Cruce; Argentina
Fil: Fuentes, Patricio. Universidad de Chile; Chile
Fil: Kochen, Silvia. Hospital El Cruce; Argentina. Universidad Nacional Arturo Jauretche; Argentina
Fil: Brusco, Luis Ignacio. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ruiz, Agustín. Universitat Internacional de Catalunya; España. Instituto de Salud Carlos III; España
Fil: Morelli, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Achitte, Eduardo Alfredo. University of Cologne; Alemania. University of Bonn Medical Center; Alemania - Materia
-
ADMIXTURE
GENETIC RISK SCORE
GENETICS
GENOME-WIDE ASSOCIATION STUDY
HISPANIC
LATIN AMERICA
NATIVE-AMERICAN ANCESTRY
SOUTH AMERICA - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/252883
Ver los metadatos del registro completo
| id |
CONICETDig_1e5810f5c90658f5e7eecd46d85245ac |
|---|---|
| oai_identifier_str |
oai:ri.conicet.gov.ar:11336/252883 |
| network_acronym_str |
CONICETDig |
| repository_id_str |
3498 |
| network_name_str |
CONICET Digital (CONICET) |
| spelling |
The first genome‐wide association study in the Argentinian and Chilean populations identifies shared genetics with Europeans in Alzheimer's diseaseDalmasso, Maria Carolinade Rojas, ItziarOlivar, NatividadMuchnik, CarolinaAngel, BárbaraGloger, SergioSanchez Abalos, Mariana SoledadChacón, María VictoriaAránguiz, RafaelOrellana, PaulinaCuesta, CarolinaGaleano, PabloCampanelli, LorenzoNovack, Gisela VaninaMartinez, Luis EduardoMedel, Nancy RuthLisso, JulietaSevillano, Zulma HaidéeIrureta, NicolásCastaño, Eduardo MiguelMontrreal, LauraThoenes, MichaelaHanses, ClaudiaHeilmann-Heimbach, StefanieFuentes, PatricioKochen, SilviaBrusco, Luis IgnacioRuiz, AgustínMorelli, LauraAchitte, Eduardo AlfredoADMIXTUREGENETIC RISK SCOREGENETICSGENOME-WIDE ASSOCIATION STUDYHISPANICLATIN AMERICANATIVE-AMERICAN ANCESTRYSOUTH AMERICAhttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3INTRODUCTION Genome-wide association studies (GWAS) are fundamental for identifying loci associated with diseases. However, they require replication in other ethnicities. METHODS We performed GWAS on sporadic Alzheimer's disease (AD) including 539 patients and 854 controls from Argentina and Chile. We combined our results with those from the European Alzheimer and Dementia Biobank (EADB) in a meta-analysis and tested their genetic risk score (GRS) performance in this admixed population. RESULTS We detected apolipoprotein E ε4 as the single genome-wide significant signal (odds ratio = 2.93 [2.37–3.63], P = 2.6 × 10−23). The meta-analysis with EADB summary statistics revealed four new loci reaching GWAS significance. Functional annotations of these loci implicated endosome/lysosomal function. Finally, the AD-GRS presented a similar performance in these populations, despite the score diminished when the Native American ancestry rose. DISCUSSION We report the first GWAS on AD in a population from South America. It shows shared genetics modulating AD risk between the European and these admixed populations. Highlights This is the first genome-wide association study on Alzheimer's disease (AD) in a population sample from Argentina and Chile. Trans-ethnic meta-analysis reveals four new loci involving lysosomal function in AD. This is the first independent replication for TREM2L, IGH-gene-cluster, and ADAM17 loci. A genetic risk score (GRS) developed in Europeans performed well in this population. The higher the Native American ancestry the lower the GRS values.Fil: Dalmasso, Maria Carolina. Universidad Nacional Arturo Jauretche; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: de Rojas, Itziar. Universitat Internacional de Catalunya; España. Instituto de Salud Carlos III; EspañaFil: Olivar, Natividad. Universidad de Buenos Aires; ArgentinaFil: Muchnik, Carolina. Universidad de Buenos Aires; ArgentinaFil: Angel, Bárbara. Universidad de Buenos Aires; ArgentinaFil: Gloger, Sergio. Universidad de Chile; ChileFil: Sanchez Abalos, Mariana Soledad. Interuniversity Center For Healthy Aging; ChileFil: Chacón, María Victoria. Centro Internacional de Estudios Clinicos; ChileFil: Aránguiz, Rafael. Universidad de Chile; ChileFil: Orellana, Paulina. Hospital Regional de Ushuaia; ArgentinaFil: Cuesta, Carolina. Centro Internacional de Estudios Clinicos; ChileFil: Galeano, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Campanelli, Lorenzo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Novack, Gisela Vanina. Universidad Adolfo Ibañez; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Martinez, Luis Eduardo. Hospital Interzonal General de Agudos-Eva Perón; ArgentinaFil: Medel, Nancy Ruth. Hospital Regional de Agudos Eva Perón (formerly Castex); ArgentinaFil: Lisso, Julieta. Fundacion Instituto Leloir Antigua Fundacion Campomar; ArgentinaFil: Sevillano, Zulma Haidée. Fundacion Instituto Leloir Antigua Fundacion Campomar; ArgentinaFil: Irureta, Nicolás. Fundacion Instituto Leloir Antigua Fundacion Campomar; ArgentinaFil: Castaño, Eduardo Miguel. Hospital Regional de Agudos Eva Perón (formerly Castex); ArgentinaFil: Montrreal, Laura. Hospital El Cruce; ArgentinaFil: Thoenes, Michaela. Studies In Neuroscience And Complex Systems Unit (enys-conicet-hec-unaj). Florencio Varela; ArgentinaFil: Hanses, Claudia. Studies In Neuroscience And Complex Systems Unit (enys-conicet-hec-unaj). Florencio Varela; ArgentinaFil: Heilmann-Heimbach, Stefanie. Hospital El Cruce; ArgentinaFil: Fuentes, Patricio. Universidad de Chile; ChileFil: Kochen, Silvia. Hospital El Cruce; Argentina. Universidad Nacional Arturo Jauretche; ArgentinaFil: Brusco, Luis Ignacio. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ruiz, Agustín. Universitat Internacional de Catalunya; España. Instituto de Salud Carlos III; EspañaFil: Morelli, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Achitte, Eduardo Alfredo. University of Cologne; Alemania. University of Bonn Medical Center; AlemaniaElsevier Science Inc.2023-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/252883Dalmasso, Maria Carolina; de Rojas, Itziar; Olivar, Natividad; Muchnik, Carolina; Angel, Bárbara; et al.; The first genome‐wide association study in the Argentinian and Chilean populations identifies shared genetics with Europeans in Alzheimer's disease; Elsevier Science Inc.; Alzheimers & Dementia; 20; 2; 11-2023; 1298-13081552-5260CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1002/alz.13522info:eu-repo/semantics/altIdentifier/url/https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.13522info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:39:43Zoai:ri.conicet.gov.ar:11336/252883instacron: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:34982025-09-29 09:39:43.665CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
The first genome‐wide association study in the Argentinian and Chilean populations identifies shared genetics with Europeans in Alzheimer's disease |
| title |
The first genome‐wide association study in the Argentinian and Chilean populations identifies shared genetics with Europeans in Alzheimer's disease |
| spellingShingle |
The first genome‐wide association study in the Argentinian and Chilean populations identifies shared genetics with Europeans in Alzheimer's disease Dalmasso, Maria Carolina ADMIXTURE GENETIC RISK SCORE GENETICS GENOME-WIDE ASSOCIATION STUDY HISPANIC LATIN AMERICA NATIVE-AMERICAN ANCESTRY SOUTH AMERICA |
| title_short |
The first genome‐wide association study in the Argentinian and Chilean populations identifies shared genetics with Europeans in Alzheimer's disease |
| title_full |
The first genome‐wide association study in the Argentinian and Chilean populations identifies shared genetics with Europeans in Alzheimer's disease |
| title_fullStr |
The first genome‐wide association study in the Argentinian and Chilean populations identifies shared genetics with Europeans in Alzheimer's disease |
| title_full_unstemmed |
The first genome‐wide association study in the Argentinian and Chilean populations identifies shared genetics with Europeans in Alzheimer's disease |
| title_sort |
The first genome‐wide association study in the Argentinian and Chilean populations identifies shared genetics with Europeans in Alzheimer's disease |
| dc.creator.none.fl_str_mv |
Dalmasso, Maria Carolina de Rojas, Itziar Olivar, Natividad Muchnik, Carolina Angel, Bárbara Gloger, Sergio Sanchez Abalos, Mariana Soledad Chacón, María Victoria Aránguiz, Rafael Orellana, Paulina Cuesta, Carolina Galeano, Pablo Campanelli, Lorenzo Novack, Gisela Vanina Martinez, Luis Eduardo Medel, Nancy Ruth Lisso, Julieta Sevillano, Zulma Haidée Irureta, Nicolás Castaño, Eduardo Miguel Montrreal, Laura Thoenes, Michaela Hanses, Claudia Heilmann-Heimbach, Stefanie Fuentes, Patricio Kochen, Silvia Brusco, Luis Ignacio Ruiz, Agustín Morelli, Laura Achitte, Eduardo Alfredo |
| author |
Dalmasso, Maria Carolina |
| author_facet |
Dalmasso, Maria Carolina de Rojas, Itziar Olivar, Natividad Muchnik, Carolina Angel, Bárbara Gloger, Sergio Sanchez Abalos, Mariana Soledad Chacón, María Victoria Aránguiz, Rafael Orellana, Paulina Cuesta, Carolina Galeano, Pablo Campanelli, Lorenzo Novack, Gisela Vanina Martinez, Luis Eduardo Medel, Nancy Ruth Lisso, Julieta Sevillano, Zulma Haidée Irureta, Nicolás Castaño, Eduardo Miguel Montrreal, Laura Thoenes, Michaela Hanses, Claudia Heilmann-Heimbach, Stefanie Fuentes, Patricio Kochen, Silvia Brusco, Luis Ignacio Ruiz, Agustín Morelli, Laura Achitte, Eduardo Alfredo |
| author_role |
author |
| author2 |
de Rojas, Itziar Olivar, Natividad Muchnik, Carolina Angel, Bárbara Gloger, Sergio Sanchez Abalos, Mariana Soledad Chacón, María Victoria Aránguiz, Rafael Orellana, Paulina Cuesta, Carolina Galeano, Pablo Campanelli, Lorenzo Novack, Gisela Vanina Martinez, Luis Eduardo Medel, Nancy Ruth Lisso, Julieta Sevillano, Zulma Haidée Irureta, Nicolás Castaño, Eduardo Miguel Montrreal, Laura Thoenes, Michaela Hanses, Claudia Heilmann-Heimbach, Stefanie Fuentes, Patricio Kochen, Silvia Brusco, Luis Ignacio Ruiz, Agustín Morelli, Laura Achitte, Eduardo Alfredo |
| 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 |
ADMIXTURE GENETIC RISK SCORE GENETICS GENOME-WIDE ASSOCIATION STUDY HISPANIC LATIN AMERICA NATIVE-AMERICAN ANCESTRY SOUTH AMERICA |
| topic |
ADMIXTURE GENETIC RISK SCORE GENETICS GENOME-WIDE ASSOCIATION STUDY HISPANIC LATIN AMERICA NATIVE-AMERICAN ANCESTRY SOUTH AMERICA |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.4 https://purl.org/becyt/ford/3 |
| dc.description.none.fl_txt_mv |
INTRODUCTION Genome-wide association studies (GWAS) are fundamental for identifying loci associated with diseases. However, they require replication in other ethnicities. METHODS We performed GWAS on sporadic Alzheimer's disease (AD) including 539 patients and 854 controls from Argentina and Chile. We combined our results with those from the European Alzheimer and Dementia Biobank (EADB) in a meta-analysis and tested their genetic risk score (GRS) performance in this admixed population. RESULTS We detected apolipoprotein E ε4 as the single genome-wide significant signal (odds ratio = 2.93 [2.37–3.63], P = 2.6 × 10−23). The meta-analysis with EADB summary statistics revealed four new loci reaching GWAS significance. Functional annotations of these loci implicated endosome/lysosomal function. Finally, the AD-GRS presented a similar performance in these populations, despite the score diminished when the Native American ancestry rose. DISCUSSION We report the first GWAS on AD in a population from South America. It shows shared genetics modulating AD risk between the European and these admixed populations. Highlights This is the first genome-wide association study on Alzheimer's disease (AD) in a population sample from Argentina and Chile. Trans-ethnic meta-analysis reveals four new loci involving lysosomal function in AD. This is the first independent replication for TREM2L, IGH-gene-cluster, and ADAM17 loci. A genetic risk score (GRS) developed in Europeans performed well in this population. The higher the Native American ancestry the lower the GRS values. Fil: Dalmasso, Maria Carolina. Universidad Nacional Arturo Jauretche; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: de Rojas, Itziar. Universitat Internacional de Catalunya; España. Instituto de Salud Carlos III; España Fil: Olivar, Natividad. Universidad de Buenos Aires; Argentina Fil: Muchnik, Carolina. Universidad de Buenos Aires; Argentina Fil: Angel, Bárbara. Universidad de Buenos Aires; Argentina Fil: Gloger, Sergio. Universidad de Chile; Chile Fil: Sanchez Abalos, Mariana Soledad. Interuniversity Center For Healthy Aging; Chile Fil: Chacón, María Victoria. Centro Internacional de Estudios Clinicos; Chile Fil: Aránguiz, Rafael. Universidad de Chile; Chile Fil: Orellana, Paulina. Hospital Regional de Ushuaia; Argentina Fil: Cuesta, Carolina. Centro Internacional de Estudios Clinicos; Chile Fil: Galeano, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Campanelli, Lorenzo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Novack, Gisela Vanina. Universidad Adolfo Ibañez; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Martinez, Luis Eduardo. Hospital Interzonal General de Agudos-Eva Perón; Argentina Fil: Medel, Nancy Ruth. Hospital Regional de Agudos Eva Perón (formerly Castex); Argentina Fil: Lisso, Julieta. Fundacion Instituto Leloir Antigua Fundacion Campomar; Argentina Fil: Sevillano, Zulma Haidée. Fundacion Instituto Leloir Antigua Fundacion Campomar; Argentina Fil: Irureta, Nicolás. Fundacion Instituto Leloir Antigua Fundacion Campomar; Argentina Fil: Castaño, Eduardo Miguel. Hospital Regional de Agudos Eva Perón (formerly Castex); Argentina Fil: Montrreal, Laura. Hospital El Cruce; Argentina Fil: Thoenes, Michaela. Studies In Neuroscience And Complex Systems Unit (enys-conicet-hec-unaj). Florencio Varela; Argentina Fil: Hanses, Claudia. Studies In Neuroscience And Complex Systems Unit (enys-conicet-hec-unaj). Florencio Varela; Argentina Fil: Heilmann-Heimbach, Stefanie. Hospital El Cruce; Argentina Fil: Fuentes, Patricio. Universidad de Chile; Chile Fil: Kochen, Silvia. Hospital El Cruce; Argentina. Universidad Nacional Arturo Jauretche; Argentina Fil: Brusco, Luis Ignacio. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Ruiz, Agustín. Universitat Internacional de Catalunya; España. Instituto de Salud Carlos III; España Fil: Morelli, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Achitte, Eduardo Alfredo. University of Cologne; Alemania. University of Bonn Medical Center; Alemania |
| description |
INTRODUCTION Genome-wide association studies (GWAS) are fundamental for identifying loci associated with diseases. However, they require replication in other ethnicities. METHODS We performed GWAS on sporadic Alzheimer's disease (AD) including 539 patients and 854 controls from Argentina and Chile. We combined our results with those from the European Alzheimer and Dementia Biobank (EADB) in a meta-analysis and tested their genetic risk score (GRS) performance in this admixed population. RESULTS We detected apolipoprotein E ε4 as the single genome-wide significant signal (odds ratio = 2.93 [2.37–3.63], P = 2.6 × 10−23). The meta-analysis with EADB summary statistics revealed four new loci reaching GWAS significance. Functional annotations of these loci implicated endosome/lysosomal function. Finally, the AD-GRS presented a similar performance in these populations, despite the score diminished when the Native American ancestry rose. DISCUSSION We report the first GWAS on AD in a population from South America. It shows shared genetics modulating AD risk between the European and these admixed populations. Highlights This is the first genome-wide association study on Alzheimer's disease (AD) in a population sample from Argentina and Chile. Trans-ethnic meta-analysis reveals four new loci involving lysosomal function in AD. This is the first independent replication for TREM2L, IGH-gene-cluster, and ADAM17 loci. A genetic risk score (GRS) developed in Europeans performed well in this population. The higher the Native American ancestry the lower the GRS values. |
| publishDate |
2023 |
| dc.date.none.fl_str_mv |
2023-11 |
| 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/11336/252883 Dalmasso, Maria Carolina; de Rojas, Itziar; Olivar, Natividad; Muchnik, Carolina; Angel, Bárbara; et al.; The first genome‐wide association study in the Argentinian and Chilean populations identifies shared genetics with Europeans in Alzheimer's disease; Elsevier Science Inc.; Alzheimers & Dementia; 20; 2; 11-2023; 1298-1308 1552-5260 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/252883 |
| identifier_str_mv |
Dalmasso, Maria Carolina; de Rojas, Itziar; Olivar, Natividad; Muchnik, Carolina; Angel, Bárbara; et al.; The first genome‐wide association study in the Argentinian and Chilean populations identifies shared genetics with Europeans in Alzheimer's disease; Elsevier Science Inc.; Alzheimers & Dementia; 20; 2; 11-2023; 1298-1308 1552-5260 CONICET Digital CONICET |
| dc.language.none.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.1002/alz.13522 info:eu-repo/semantics/altIdentifier/url/https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.13522 |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-nd/2.5/ar/ |
| eu_rights_str_mv |
openAccess |
| rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/ |
| dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf |
| dc.publisher.none.fl_str_mv |
Elsevier Science Inc. |
| publisher.none.fl_str_mv |
Elsevier Science Inc. |
| dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
| reponame_str |
CONICET Digital (CONICET) |
| collection |
CONICET Digital (CONICET) |
| instname_str |
Consejo Nacional de Investigaciones Científicas y Técnicas |
| repository.name.fl_str_mv |
CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
| repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
| _version_ |
1844613257200926720 |
| score |
13.070432 |