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| DOI | 10.1002/ALZ.093055 | ||
| Año | 2024 | ||
| Tipo |
Citas Totales
Autores Afiliación Chile
Instituciones Chile
% Participación
Internacional
Autores
Afiliación Extranjera
Instituciones
Extranjeras
BACKGROUND: Most research initiatives have emerged from high-income countries (HIC), leaving a gap in understanding the disease's genetic basis in diverse populations like those in Latin American countries (LAC). ReDLat tackles this gap, focusing on LAC's unique genetics and socioeconomic factors to identify specific Alzheimer's Disease (AD) and Frontotemporal Dementia (FTD) risk factors in Mexico, Colombia, Peru, Chile, Argentina, and Brazil. METHOD: We employed a comprehensive genetic analysis approach, integrating Whole Genome Sequencing (WGS), Exome Sequencing, and SNP arrays to understand the cohort's unique genetic architecture. We conducted ancestry analysis and searched for disease-causing variants with mendelian inheritance, genome-wide association studies (GWAS), rare variant enrichment, and evaluation of Polygenic Risk Scores (PRS). RESULTS: We recruited and genotyped an initial cohort of 1046 participants with AD, 423 with FTD, and 855 healthy controls (HC) between 2020 and 2023. Analysis is ongoing, and we expect to sequence ∼600 additional samples in the coming months. Ancestry analysis revealed tri-continental admixture, except for Brazil, which showed an additional Asian component (Figure 1). Top candidate gene rare variant enrichment associations (SKAT p < 0.05) were TREM2 for FTD and ABCA7 and ABCA1 for AD. GWAS identified a robust association with the APOE locus on chromosome 19 in AD vs. HC.. We tested an AD PRS developed in European populations by Bellenguez et al (2020). on our cohort using 83 single-nucleotide polymorphisms.. The PRS modestly distinguishes between all patients and HC (p = 2.4 × 10^-12), AD vs. HC (p = 2.2 × 10^-12), and even FTD vs. HC (p = 4.3 × 10^-5), albeit with modest separation between groups, as expected for its application in a genetically admixed population. CONCLUSION: Our findings represent a pivotal step in understanding the genetic landscape of AD and FTD in admixed populations. They underscore the importance of including diverse populations in genetic research, paving the way for future studies. These findings have the potential to inform more personalized approaches to the diagnosis and treatment of neurodegenerative diseases in diverse global populations, as well as identify novel targets for therapeutic development.
| Ord. | Autor | Género | Institución - País |
|---|---|---|---|
| 1 | Acosta-Uribe, Juliana | - |
University of California, Santa Barbara - Estados Unidos
Universidad de Antioquia - Colombia |
| 2 | Escudero, Stefanie Danielle Pina | - |
University of California, San Francisco - Estados Unidos
|
| 3 | Cochran, J. Nicholas | - |
HudsonAlpha Institute for Biotechnology - Estados Unidos
|
| 4 | Taylor, Jared W. | - |
HudsonAlpha Institute for Biotechnology - Estados Unidos
|
| 5 | Solsberg, Caroline Warly | - |
University of California, San Francisco - Estados Unidos
|
| 6 | Matallana, Diana L. | Mujer |
Pontificia Universidad Javeriana - Colombia
Hospital Universitario San Ignacio - Colombia Fundación Santa Fe de Bogotá - Colombia |
| 7 | Takada, Leonel T. | Hombre |
Universidade de São Paulo - Brasil
|
| 8 | Bruno, Martin Alejandro | - |
Universidad Nacional de San Juan - Argentina
Consejo Nacional de Investigaciones Científicas y Técnicas - Argentina |
| 9 | Levine, Alexandra R. | - |
University of California, Santa Barbara - Estados Unidos
|
| 10 | George, Dawwod S. | - |
University of California, Santa Barbara - Estados Unidos
|
| 11 | Lopera, Francisco | Hombre |
Universidad de Antioquia - Colombia
|
| 12 | Chonchol, Andrea Slachevsky | - |
Universidad del Desarrollo - Chile
Universidad de Chile - Chile Centro de Gerociencia, Salud Mental y Metabolismo - Chile |
| 13 | Behrens, Maria I. | Mujer |
Hospital Clínico Universidad de Chile - Chile
|
| 14 | Funes, José Alberto Ávila | - |
Instituto Nacional de la Nutrición Salvador Zubiran - México
|
| 15 | Zapata-Restrepo, Lina Maria | - |
Universidad Icesi - Colombia
Fundación Valle del Lili - Colombia |
| 16 | Brusco, Luis Ignacio | Hombre |
ALZAR - Argentine Alzheimer's Association - Argentina
Universidad de Buenos Aires - Argentina |
| 17 | Custodio, Nilton | - |
Instituto Peruano de Neurociencias - Perú
|
| 18 | Franco, Teresita Ramos | - |
Universidad de Chile - Chile
|
| 19 | Bruna, Bárbara | - |
Hospital Clínico Universidad de Chile - Chile
|
| 20 | PONCE-RAMIREZ, DANIELA PATRICIA | Mujer |
Hospital Clínico Universidad de Chile - Chile
|
| 21 | Gelvez, Nancy | - |
Pontificia Universidad Javeriana - Colombia
|
| 22 | Lopez, Greizy | - |
Pontificia Universidad Javeriana - Colombia
|
| 23 | Gomez, Luisa | - |
Pontificia Universidad Javeriana - Colombia
|
| 24 | Buitrago, Carlos Felipe | - |
Pontificia Universidad Javeriana - Colombia
|
| 25 | Reyes, Pablo A. | - |
Pontificia Universidad Javeriana - Colombia
|
| 26 | Durón, Dafne Estefania | - |
Instituto Nacional de la Nutrición Salvador Zubiran - México
|
| 27 | Pantazis, Caroline | - |
National Institute on Aging (NIA) - Estados Unidos
|
| 28 | Maito, Marcelo Adrian | - |
Universidad Adolfo Ibáñez - Chile
|
| 29 | Javandel, Shireen | Mujer |
University of California, San Francisco - Estados Unidos
|
| 30 | Godoy, Maria Eugenia | Mujer |
Universidad de San Andrés - Argentina
|
| 31 | Millon, Maria Beatriz Bistue | - |
Universidad Católica de Cuyo - Argentina
Consejo Nacional de Investigaciones Científicas y Técnicas - Argentina |
| 32 | Vitale, Dan | - |
Data Tecnica International - Estados Unidos
|
| 33 | Nalls, Mike A. | - |
Data Tecnica International - Estados Unidos
|
| 34 | Singleton, Andrew B. | Hombre |
National Institute on Aging (NIA) - Estados Unidos
|
| 35 | Miller, Bruce | Hombre |
University of California, San Francisco - Estados Unidos
Global Brain Health Institute - Estados Unidos |
| 36 | LEGAZ, AGUSTINA | Mujer |
BrainLat Institute - Chile
Trinity College Dublin - Irlanda |
| 37 | Kosik, Kenneth S. | Hombre |
University of California, Santa Barbara - Estados Unidos
|
| 38 | Yokoyama, Jennifer S. | Mujer |
University of California, San Francisco - Estados Unidos
|
| 39 | Montesinos, Rosa | Mujer |
Instituto Peruano de Neurociencias - Perú
|
| 40 | Resende, Elisa de Paula Franca | Mujer |
Faculdade de Ciências Médicas de Minas Gerais - Brasil
University of California, San Francisco - Estados Unidos |