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

DALMASSO, MC; DE ROJAS, ITZIAR; CASTAÑO EM

Alzheimer's and Dementia

John Wiley and Sons Inc

Lugar: Hoboken; Año: 2023 vol. 20 p. 1298 - 1308

INTRODUCTIONGenome-wide association studies (GWAS) are fundamental for identifying loci associated with diseases. However, they require replication in other ethnicities.METHODSWe 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.RESULTSWe 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.DISCUSSIONWe 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.HighlightsThis 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.