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First GWAS on Alzheimer's Disease in Argentina and Chile populations

Dalmasso, M. C.; de Rojas, I.; Olivar, N.; Muchnik, C.; Angel, B.; Gloger, S.; Sanchez Abalos, M. S.; Chacon, M. V.; Aranguiz, R.; Orellana, P.; Cuesta, C.; Galeano, P.; Campanelli, L.; Novack, G. V.; Martinez, L. E.; Medel, N.; Lisso, J.; Sevillano, Z.; Irureta, N.; Castano, 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.; EADB, ; Lambert, J.-C.; Solis, P.; Gustavo Politis, D.; Mangone, C. A.; Gonzalez-Billault, C.; Boada, M.; Tarraga, L.; Slachevsky, A.; Albala, C.; Fu

2023-01-18 genetic and genomic medicine
10.1101/2023.01.16.23284609 medRxiv
Show abstract

INTRODUCTIONGenome-wide association studies (GWAS) are fundamental for identifying loci associated with diseases. However, they require replication in other ethnicities. METHODSwe performed a GWAS on sporadic Alzheimers disease (AD) including 540 patients and 852 controls from Argentina and Chile. We explored the variants associated with AD in European GWAS from European Alzheimers and Dementia Biobank (EADB) and tested their genetic risk score (GRS) performance in this admixed population. RESULTSwe detected APOE4 as single genome-wide significant signal (OR=2.93[2.37-3.63], p=2.6x10-23), and fifteen additional suggestive signals previously undetected. Nine of the 83 variants reported by EADB in Europeans were replicated, and the AD-GRS presented similar performance in this Latin population, despite the score diminishes when the Native American ancestry rises. DISCUSSIONwe report the first GWAS on AD in a population from South America. It shows shared genetics that modulate AD risk between the European and the Latin American populations.

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