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The first genome‐wide association study in the Argentinian and Chilean populations identifies shared genetics with Europeans in Alzheimer's disease
Journal
Alzheimer's & Dementia
ISSN
1552-5260
1552-5279
Date Issued
2023
Author(s)
Maria Carolina Dalmasso
Itziar de Rojas
Natividad Olivar
Carolina Muchnik
Bárbara Angel
Sergio Gloger
Mariana Soledad Sanchez Abalos
María Victoria Chacón
Rafael Aránguiz
Carolina Cuesta
Pablo Galeano
Lorenzo Campanelli
Gisela Vanina Novack
Luis Eduardo Martinez
Nancy Medel
Julieta Lisso
Zulma Sevillano
Nicolás Irureta
Eduardo Miguel Castaño
Laura Montrreal
Michaela Thoenes
Claudia Hanses
Stefanie Heilmann‐Heimbach
Claudia Kairiyama
Inés Mintz
Ivana Villella
Fabiana Rueda
Amanda Romero
Nancy Wukitsevits
Ivana Quiroga
Cristian Gona
Jean‐Charles Lambert
Patricia Solis
Daniel Gustavo Politis
Carlos Alberto Mangone
Christian Gonzalez‐Billault
Mercè Boada
Lluís Tàrraga
Cecilia Albala
Patricio Fuentes
Silvia Kochen
Luis Ignacio Brusco
Agustín Ruiz
Laura Morelli
Alfredo Ramírez
Type
Resource Types::text::journal::journal article
Abstract
<jats:title>Abstract</jats:title><jats:sec><jats:title>INTRODUCTION</jats:title><jats:p>Genome‐wide association studies (GWAS) are fundamental for identifying loci associated with diseases. However, they require replication in other ethnicities.</jats:p></jats:sec><jats:sec><jats:title>METHODS</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p>We detected apolipoprotein E ε4 as the single genome‐wide significant signal (odds ratio = 2.93 [2.37–3.63], <jats:italic>P</jats:italic> = 2.6 × 10<jats:sup>−23</jats:sup>). 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.</jats:p></jats:sec><jats:sec><jats:title>DISCUSSION</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Highlights</jats:title><jats:p><jats:list list-type="bullet">
<jats:list-item><jats:p>This is the first genome‐wide association study on Alzheimer's disease (AD) in a population sample from Argentina and Chile.</jats:p></jats:list-item>
<jats:list-item><jats:p>Trans‐ethnic meta‐analysis reveals four new loci involving lysosomal function in AD.</jats:p></jats:list-item>
<jats:list-item><jats:p>This is the first independent replication for <jats:italic>TREM2L</jats:italic>, <jats:italic>IGH‐gene‐cluster</jats:italic>, and <jats:italic>ADAM17</jats:italic> loci.</jats:p></jats:list-item>
<jats:list-item><jats:p>A genetic risk score (GRS) developed in Europeans performed well in this population.</jats:p></jats:list-item>
<jats:list-item><jats:p>The higher the Native American ancestry the lower the GRS values.</jats:p></jats:list-item>
</jats:list></jats:p></jats:sec>
Scopus© citations
3
Acquisition Date
Aug 8, 2024
Aug 8, 2024