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Cited by 28Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchGenetic Associations and Epidemiology

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

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Dalmasso, Maria Carolina, de Rojas, Itziar, Olivar, Natividad, Muchnik, Carolina, Angel, Bárbara, Gloger, Sergio, Sanchez Abalos, Mariana Soledad, Chacón, María Victoria +39 more·2024·Alzheimer's & Dementia
DOI 10.1002/alz.13522PMC PMC10917041
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Abstract

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.

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Authors
Dalmasso, M. C., de Rojas, I., Olivar, N., Muchnik, C., Angel, B., Gloger, S., Sanchez Abalos, M. S., Chacón, M. V., Aránguiz, R., Orellana, P., Cuesta, C., Galeano, P., Campanelli, L., Novack, G. V., Martinez, L. E., Medel, N., Lisso, J., Sevillano, Z., Irureta, N., Castaño, E. M., Montrreal, L., Thoenes, M., Hanses, C., Heilmann‐Heimbach, S., Kairiyama, C., Mintz, I., Villella, I., Rueda, F., Romero, A., Wukitsevits, N., Quiroga, I., Gona, C., Lambert, J., Solis, P., Politis, D. G., Mangone, C. A., Gonzalez‐Billault, C., Boada, M., Tàrraga, L., Slachevsky, A., Albala, C., Fuentes, P., Kochen, S., Brusco, L. I., Ruiz, A., Morelli, L., & Ramírez, A.
Affiliations
  • Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
  • Research Center and Memory Clinic, Ace Alzheimer Center Barcelona – Universitat Internacional de Catalunya Barcelona Spain
  • Universidad de Buenos Aires (AR)
  • Public Health Nutrition Unit Institute of Nutrition and Food Technology University of Chile Santiago Chile
  • University of Chile (CL)
  • Servicio de Diabetes y Metabolismo Hospital Regional de Ushuaia Ushuaia Argentina
  • Biomedica Research Group Centro de Estudios Clínicos Santiago Chile
  • Adolfo Ibáñez University (CL)
  • Hospital Interzonal General de Agudos‐Eva Perón San Martín Argentina
  • Fundación Instituto Leloir (AR)
  • Universitat Internacional de Catalunya (ES)
  • University of Cologne (DE)
  • University Hospital Bonn (DE)
  • University of Bonn (DE)
  • Hospital El Cruce (AR)
  • Inserm (FR)
  • Hospital Donación Francisco Santojanni (AR)
  • Geroscience Center for Brain Health and Metabolism Santiago Chile
  • Universidad del Desarrollo (CL)
  • Hospital del Salvador (CL)
  • Division of Neurogenetics and Molecular Psychiatry Department of Psychiatry and Psychotherapy Faculty of Medicine and University Hospital Cologne University of Cologne Cologne Germany
Corresponding author
Morelli, Laura
ORCID
Venue
Alzheimer's & Dementia
Publisher
Wiley
Published
2023-11-20
Volume
20
Issue
2
Pages
1298-1308
ISSN
  • 1552-5260 (ISSN-L)
  • 1552-5279
DOI
10.1002/alz.13522
PMC
PMC10917041
OpenAlex
W4388851038
Cited by
28
References
42
Citations by year
2026: 11 · 2025: 11 · 2024: 4 · 2023: 2
FWCI
1.00
Type
journal article
Language
en
Open access
Licence
Locations
  • Alzheimer s & Dementia (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Conicet (publishedVersion, cc-by-nc-nd)
  • Kölner Universitäts PublikationsServer (Universität zu Köln) (submittedVersion)
  • DZNE Pub (submittedVersion, cc-by-nc-nd)
  • Universidad de Chile (submittedVersion, cc-by-nc-nd)
Funders
  • Instituto de Salud Carlos III (FI20/00215)
  • Consejo Nacional de Investigaciones Científicas y Técnicas
  • Agencia Nacional de Promoción Científica y Tecnológica (PUE060, PICTO‐2021‐UCTH00005, PICTO‐2021‐UCTH00006, PID‐2011‐0059, PIBT/09‐2013, PICT‐2016‐4647, PICT2019‐0656)
  • Alexander von Humboldt-Stiftung
  • International Society for Neurochemistry
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords
Alzheimer's disease, sporadic Alzheimer's disease
MeSH terms
Alzheimer Disease, Azides, Chile, Humans, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Genome-Wide Association Study

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