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

DALMASSO, MARIA CAROLINA; DE ROJAS, ITZIAR; OLIVAR, NATIVIDAD; MUCHNIK, CAROLINA; ANGEL, BÁRBARA; GLOGER, SERGIO; SANCHEZ ABALOS, MARIANA SOLEDAD; CHACÓN, M. 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, CRISTINA; 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

ALZHEIMERS & DEMENTIA

ELSEVIER SCIENCE INC

Lugar: Amsterdam; Año: 2024 vol. 20 p. 1298 - 1308

1552-5260

INTRODUCTION, Genome wide association studies (GWAS) are fundamental for identifying loci associated with diseases. However, they require replication in other ethnicities. METHODS, we performed GWAS on sporadic Alzheimers 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 APOE4 as the single genome wide significant signal (OR=2.93[2.37-3.63], p= 2.6x10-23 ). The meta analysis with EADB summary statistics revealed four new loci reaching GWAS significance. Functional annotations of these loci implicated endosome and 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.