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, 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
Аннотация
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.