The first genome‐wide association study in the Argentinian and Chilean populations identifies shared genetics with Europeans in Alzheimer's disease

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 Ch...

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Published in:	Alzheimer's & dementia Vol. 20; no. 2; pp. 1298 - 1308
Main Authors:	Dalmasso, Maria Carolina, 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, Lisso, Julieta, Sevillano, Zulma, Irureta, Nicolás, Castaño, Eduardo Miguel, Montrreal, Laura, Thoenes, Michaela, Hanses, Claudia, Heilmann‐Heimbach, Stefanie, Kairiyama, Claudia, Mintz, Inés, Villella, Ivana, Rueda, Fabiana, Romero, Amanda, Wukitsevits, Nancy, Quiroga, Ivana, Gona, Cristian, Lambert, Jean‐Charles, Solis, Patricia, Politis, Daniel Gustavo, Mangone, Carlos Alberto, Gonzalez‐Billault, Christian, Boada, Mercè, Tàrraga, Lluís, Slachevsky, Andrea, Albala, Cecilia, Fuentes, Patricio, Kochen, Silvia, Brusco, Luis Ignacio, Ruiz, Agustín, Morelli, Laura, Ramírez, Alfredo
Format:	Journal Article
Language:	English
Published:	United States John Wiley & Sons, Inc 01-02-2024 John Wiley and Sons Inc
Subjects:	admixture Alzheimer Disease - genetics Alzheimer's disease American Indians Apolipoproteins Associations Azides Biobanks Chile Dementia Disease Ethics Genetic Predisposition to Disease - genetics genetic risk score Genetic susceptibility Genetic testing Genetics Genome-Wide Association Study Genomes Genomics Health risk assessment Hispanic Hospitals Humans Latin America Native‐American ancestry Older people Polymorphism, Single Nucleotide - genetics Population Precision medicine Quality control South America Chile Argentina Spain Latin America South America genetics admixture genome-wide association study genetic risk score Native-American ancestry Hispanic Latin America
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Summary:	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.
Bibliography:	Itziar de Rojas and Maria Carolina Dalmasso contributed equally to this work. Agustín Ruiz, Laura Morelli and Alfredo Ramírez jointly supervised this work. ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	1552-5260 1552-5279 1552-5279
DOI:	10.1002/alz.13522